Molecular drivers of human cerebral cortical evolution

G Model NSR-4289; No. of Pages 14

ARTICLE IN PRESS Neuroscience Research xxx (2019) xxx–xxx

Contents lists available at ScienceDirect

Neuroscience Research journal homepage: www.elsevier.com/locate/neures

Review article

Molecular drivers of human cerebral cortical evolution夽 Ikuo K. Suzuki a,b,c,d,∗ a

Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 Japan VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium c Department of Neurosciences, Leuven Brain Institute, KULeuven, 3000 Leuven, Belgium d Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium b

a r t i c l e

i n f o

Article history: Received 28 March 2019 Received in revised form 30 May 2019 Accepted 31 May 2019 Available online xxx Keywords: Evolution Cerebral cortex Corticogenesis Development Neurogenesis Neural progenitor Gene duplication Regulatory evolution De novo genes NOTCH2NL

a b s t r a c t One of the most important questions in human evolutionary biology is how our ancestor has acquired an expanded volume of the cerebral cortex, which may have significantly impacted on improving our cognitive abilities. Recent comparative approaches have identified developmental features unique to the human or hominid cerebral cortex, not shared with other animals including conventional experimental models. In addition, genomic, transcriptomic, and epigenomic signatures associated with human- or hominid-specific processes of the cortical development are becoming identified by virtue of technical progress in the deep nucleotide sequencing. This review discusses ontogenic and phylogenetic processes of the human cerebral cortex, followed by the introduction of recent comprehensive approaches identifying molecular mechanisms potentially driving the evolutionary changes in the cortical development. © 2019 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

Contents 1. 2.

3.

4.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Ontology and phylogeny of the mammalian cerebral cortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2.1. Evolutionary origin and diversification of the mammalian cerebral cortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2.2. Developmental processes of the mammalian cerebral cortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Genetic signatures potentially driving human cortical evolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 3.1. HS pattern of gene expression and their regulatory evolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 3.2. Evolution of the corticogenesis-related genes in protein level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 3.2.1. HS changes in alternative splicing pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 3.2.2. HS evolution of protein sequence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 3.3. HS gene repertory involved in cortical development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 3.3.1. HS de novo transcripts and proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 3.3.2. HS genes originated by genomic segmental duplication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

夽 Review article for the Japan Neuroscience Society Young Investigator Award 2019. ∗ Corresponding author at: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 Japan. E-mail address: [email protected] https://doi.org/10.1016/j.neures.2019.05.007 0168-0102/© 2019 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

Please cite this article in press as: I.K. Suzuki, Molecular drivers of human cerebral cortical evolution. Neurosci. Res. (2019), https://doi.org/10.1016/j.neures.2019.05.007

G Model NSR-4289; No. of Pages 14

ARTICLE IN PRESS I.K. Suzuki / Neuroscience Research xxx (2019) xxx–xxx

2

1. Introduction The complex circuit embedded in an immensely enlarged volume of the cerebral cortex constitutes the neural source of cognitive abilities characterizing the human (Hill and Walsh, 2005; Lui et al., 2011; Rakic, 2009; Wilsch-Brauninger et al., 2016). The mammalian species have a huge diversity in the volume and complexity of the cerebral cortex (Herculano-Houzel, 2009; Lewitus et al., 2014; Lui et al., 2011), and the hominids, especially the human, demonstrate an exceptionally expanded volume of the cerebral cortex (Herculano-Houzel, 2017, 2009). The number of neurons principally determines the cortical volume (Cahalane et al., 2014; Herculano-Houzel, 2017), accordingly, it is essential to study the developmental regulation of neurogenesis in order to understand the evolutionary mechanism of cortical expansion. The prolonged duration of neuron production and maturation also characterizes human cortical development (Defelipe, 2011; Petanjek et al., 2011; Somel et al., 2009; Zhu et al., 2018), therefore another useful viewpoint is the evolutionary specification of temporal regulation of cortical development in the human lineage (Clancy et al., 2001; Workman et al., 2013). The molecular mechanisms responsible for the human or hominid-specific (HS) features of the cerebral cortex remains largely unknown, however, significant progress has been made recently, specially attributed to large-scale “omics” studies. The gene expression changes and the regulatory changes behind of them, the mutations changing protein structure, and the changes of a gene repertoire, have been reported to potentially drive the HS pattern of cortical development. This review introduces these recently identified genetic mechanisms potentially driving human cortical evolution.

fates do exit in the developing avian and reptilian telencephalon, but are surprisingly distributed in the medial and lateral domains in the non-mammalian animals, respectively (Fig. 1A and B) (Briscoe et al., 2018; Briscoe and Ragsdale, 2018; Dugas-Ford et al., 2012; Lein et al., 2017; Nomura et al., 2008; Suzuki et al., 2012; Suzuki and Hirata, 2014). These observations propose a novel evolutionary scenario, whereby the cellular origin of the mammalian cortical neurons predates the evolutionary appearance of a first mammal (Fig. 1C) (Suzuki and Hirata, 2013, 2012). This proposal will be tested in the future by the comprehensive comparison of cell types in the developing brains of diverse non-mammalian animals, such as by single-cell transcriptomics of differentiating cell types from stem cell populations (Arendt, 2008; Arendt et al., 2016; Marioni and Arendt, 2017; Telley et al., 2018, 2016). The precise evolutionary process originating the layered mammalian cerebral cortex remains unanswered and the separated discussion about the cellular origin of neuronal subtypes and the structural origin of their layered arrangement is meaningful. During the mammalian evolutionary diversification, the morphology of the cerebral cortex has been further modified with keeping a common layer structure. For example, in the course of primate evolution toward the human, the cortical surface has been massively expanded, highly folded i.e. gyrificated, and further subdivided into more functionally distinct areas (Fig. 1D) (Kaas, 2011; Kelava et al., 2013; Krubitzer, 2007; Lewitus et al., 2014; Lui et al., 2011). The evolutionary expansion of the cortical surface area increases the number of cortical columns, possibly leading to the empowerment of information processing and plasticity (Geschwind and Rakic, 2013; Rakic, 1995). 2.2. Developmental processes of the mammalian cerebral cortex

2. Ontology and phylogeny of the mammalian cerebral cortex 2.1. Evolutionary origin and diversification of the mammalian cerebral cortex The cerebral cortex has been regarded as an evolutionary new brain region, which has been originated in the early mammals because its internal structure is highly conserved among the mammalian species, but no brain regions showing the similar structure have been found in the non-mammalian animals. The cerebral cortex is the dorsal region of the mammalian telencephalon showing a characteristic neuronal distribution in multiple tangential layers (Fig. 1A). Although there are recognizable differences, the layer pattern is largely consistent through different areas in a given organism and is also phylogenetically conserved in virtually all mammalian species, including the most basal monotremes (Hassiotis et al., 2005; Hassiotis and Ashwell, 2003). The laminar arrangement of neurons provides a structural basis of a columnar circuit, which works as a unit of information processing in the mammalian cortex (Hubel and Wiesel, 1969, 1963; Katz and Crowley, 2002). Interestingly, the cortical layer structure is a mammalian evolutionary innovation; only the mammalian species share a highly conserved layer pattern, but the non-mammalian animals, such as the birds and the reptiles, show nuclear structures in their cortical counterparts (Fig. 1B). In non-mammalian animals, a neuron subtype sharing similar characteristics is assembled in a discrete nucleus or domain, instead of a layer (Jarvis et al., 2013; Lein et al., 2017; Northcutt and Kaas, 1995). Although many attempts were failed to demonstrate clear one-to-one regional or cell type homology between the mammalian cortex and the non-mammalian counterparts in the adult (Belgard et al., 2013; Belgard and Montiel, 2013; Chen et al., 2013; Jacobi et al., 2018; Jarvis et al., 2005; Montiel and Molnár, 2013), it was shown that neuronal subtypes expressing molecular determinants of the mammalian deep and upper layer

Human has acquired an extraordinarily enlarged volume of cerebral cortex in the last 2 million years of evolution (Du et al., 2018; Montgomery, 2018), which is occupied by 100 billion neurons (Herculano-Houzel, 2017, 2009). The difference in the cortical volume between the human and the non-human species is already evident at the early developmental timing and is gradually enlarged as development proceeds (Altman and Bayer, 2015; Bayer et al., 1993; Sakai et al., 2013, 2012, 2011), suggesting that humanspecific developmental processes produce a larger number of neurons and consequently expand cortical volume. At the time when the future cerebral cortex is specified in the anterior neural tube, the neuroepithelial (NE) cells amplify themselves by symmetric proliferative division and form a sheet of the founder stem cell population of cortical neurons and glia (Fig. 2A). Subsequently, the NE cells begin producing differentiated neurons and more committed progenitors by asymmetric cell division, and they are called as the radial glia (RG). The undifferentiated RG progenitors are maintained in an undifferentiated state for a certain period and sequentially generate multiple excitatory subtypes of neurons in an inside-out direction; the subtypes in the deeper layers are produced earlier than those in the upper layers. The temporal regulation of cortical progenitors to produce a certain subtype of neuron in a given developmental timing are increasingly understood (Desai and McConnell, 2000; Greig et al., 2013; Hirabayashi and Gotoh, 2010; Leone et al., 2008; McConnell, 1991; McConnell and Kaznowski, 1991; Miyata et al., 2010; Mizutani and Saito, 2005; Oberst et al., 2018; Okamoto et al., 2016; Vitali et al., 2018; Yoon et al., 2017). Every single RG cell in mice produces a relatively constant number of descendant neurons allocated in multiple cortical layers regardless of its tangential position (Gao et al., 2014). Although equivalent quantitative in vivo clonal studies in the primates have never been conducted so far, human RG cell was reported to have a potential to generate a larger number of neurons compared to that of a non-human primate (Otani et al., 2016),

Please cite this article in press as: I.K. Suzuki, Molecular drivers of human cerebral cortical evolution. Neurosci. Res. (2019), https://doi.org/10.1016/j.neures.2019.05.007

G Model NSR-4289; No. of Pages 14

ARTICLE IN PRESS I.K. Suzuki / Neuroscience Research xxx (2019) xxx–xxx

3

Fig. 1. Neuronal arrangement in tangential layers in the mammalian cerebral cortex (A), but in the medial and lateral domains in the avian counterpart (B). Three major subtypes of excitatory neurons, the locally connecting neurons (pink), the input receiving neurons (yellow) and the output projection neurons (green), are conserved between the mammals and the birds. (C) The hypothetical evolutionary scenario originating the mammalian cerebral cortex consisting of multiple neuron subtypes distributing in tangential layers. (D) During the mammalian evolution, in particular along the lineage toward the human, the cortical size has been gradually expanded and its surface has been folded. Images are the dorsal view of whole cerebral cortex in the same scale, except for the enlarged image of Marmoset brain (Images adapted from www. brainmuseum.org). The divergence time is taken from The Timescale of Life (www.timetree.org) (C and D). Scale bars; 1 cm.

suggesting that a greater neurogenetic capacity is intrinsically installed in the human cortical progenitors (Suzuki et al., 2018). Such higher neurogenetic potential of human cortical progenitor is partly explained by the extended duration of neurogenesis (Suzuki et al., 2018; Suzuki and Vanderhaeghen, 2015), and therefore the temporal regulation of cortical neurogenesis is reasonably an important research focus (Kageyama et al., 2019; Kawaguchi, 2019) in order to understand the evolutionary mechanism of human cortical expansion (Fig. 2B). The temporally-regulated neurogenesis of RG progenitor, whereby a single progenitor sequentially produces multiple layer subtypes by serial asymmetric divisions, is not limited to the mammals, but conserved in non-mammalian animals possessing a non-layered spatial arrangement of neuronal subtypes (Suzuki et al., 2012). This observation also supports a hypothesis of the ancient evolutionary origin of the cortical neuron subtypes before the mammalian emergence (Suzuki and Hirata, 2013, 2012).

The remaining interesting question is the regulation of RG behavior in neurogenesis behind the construction of phylogeny-specific brain structures. In the later phase of mammalian cortical neurogenesis, neurons are predominantly generated through transient amplifying progenitors in the subventricular zone (SVZ), such as the intermediate or basal progenitors (IP or BP) (Attardo et al., 2008; Haubensak et al., 2006; Kowalczyk et al., 2009; Mihalas et al., 2016; Miyata et al., 2004; Noctor et al., 2004) and the outer or basal radial glia (oRG or bRG) (Fietz et al., 2010; Hansen et al., 2010; Shitamukai et al., 2011; Wang et al., 2011), not directly from the RG progenitors in the ventricular zone (VZ) (Fig. 2C). These SVZ progenitor subtypes are divergent among the different mammalian groups, compared with RG progenitors in the VZ. Tbr2-expressing BP subtype is abundantly observed only in the placental mammals but barely detected in the non-mammals and the marsupials (Cárdenas et al., 2018;

Please cite this article in press as: I.K. Suzuki, Molecular drivers of human cerebral cortical evolution. Neurosci. Res. (2019), https://doi.org/10.1016/j.neures.2019.05.007

G Model NSR-4289; No. of Pages 14 4

ARTICLE IN PRESS I.K. Suzuki / Neuroscience Research xxx (2019) xxx–xxx

Fig. 2. (A) Temporal progression of cortical developmental processes, amplification of NE cells (1), generation of distinct layer subtypes of neurons (2), and eventually gliogenesis (3). (B) The stepwise progression of corticogenesis is highly conserved among mammalian species, however, the duration of each phase is significantly elongated in the human compared to the other species. (C) Although direct neurogenesis from RG progenitors is dominant in the earlier phase, indirect neurogenesis through transit amplifying progenitors, such as IP (or BP) and oRG (or bRG), is predominant in the later phase. Abbreviations; NE, neuroepithelial; RG, radial glia; IP, intermediate progenitor; BP, basal progenitor; oRG, outer radial glia; bRG, basal radial glia, VZ, ventricular zone; SVZ, subventricular zone; IZ, intermediate zone; CP, cortical plate.

Nomura et al., 2016; Puzzolo and Mallamaci, 2010; Sauerland et al., 2018). Another SVZ progenitor subtype oRG has been detected in a marsupial species (Sauerland et al., 2018), is relatively rare in mice and rats, possessing small and smooth cortices (Shitamukai et al., 2011; Vaid et al., 2018; Wang et al., 2011), but highly enriched in the basal part of SVZ (oSVZ) in the species possessing expanded and folded cortices (Betizeau et al., 2013; Fietz et al., 2010; GarcıaMoreno et al., 2012; Hansen et al., 2010; Hatakeyama et al., 2017). Also, in some studies using genetic alterations in mice, an increase of oRG-like progenitors is frequently observed concomitantly with the complex folding of cortical surfaces (Florio et al., 2015; Ju et al., 2016; Liu et al., 2017; Martínez-Martínez et al., 2016; Stahl et al., 2013; Wang et al., 2016), despite the known examples introducing a complex folding on cortical surface without detectable increase of oRG-like cells (Chenn and Walsh, 2002; Florio et al., 2015; Long et al., 2018; Nonaka-Kinoshita et al., 2013; Rash et al., 2013; Smith et al., 2018). The diversity and lineage relationship of distinct progenitor subtypes are actively studied in multiple animal models, including human fetal cortical slices, and highly dynamic and complex cellular behaviors have been reported (Betizeau et al., 2013; Dehay et al., 2015; Huttner et al., 2013; Kalebic et al., 2019; Lui et al., 2011; Nowakowski et al., 2017, 2016; Reillo and Borrell, 2012). The molecular signals involved in the origin and behaviors of SVZ progenitor are recently becoming identified (Cárdenas et al., 2018; Fietz et al., 2010; Ju et al., 2016; Kalebic et al., 2019; Kostic et al., 2019; Liu et al., 2017; Martínez-Martínez et al., 2016; Pollen et al., 2019; Vaid et al., 2018) and their evolutionary impact on the cortical expansion and folding is of particular interest.

sively elucidated. The evolutionary timing of their origin is variable; some of them are indeed specific to the modern human species, but the others are exclusively shared by the human and some non-human hominids. For the simplicity, the genetic signatures uniquely detected in the human and those specific to some hominid species, including the human, are termed as human- or hominidspecific (HS) features hereafter in this review, except for the special emphasis on the truly human-specific ones. HS genetic signatures can be classified into three major categories (Fig. 3A). First is the differentially expressed genes during corticogenesis in different species (Fig. 3B). Transcriptome studies confirmed that most genes, including widely used marker genes of the cell types in the developing cortex, are similarly expressed in the human and others, and therefore the remaining small fraction of genes differentially expressed in the different phyla is the center of researchers’ attention. Secondly, even among the genes commonly expressed in the human and others, a number of genes demonstrate HS changes in protein structure by an alteration in splicing pattern or by substitutions of amino acid residues (Fig. 3C). The third category is the genes uniquely present in the human or hominids (Fig. 3D). Although a great majority of genes in the human genome is shared with the other animals, it is recently becoming clear that the genes uniquely present in the human or hominid species are functionally involved in the processes of corticogenesis. The molecular mechanisms in three above-mentioned categories relevant to the HS features of corticogenesis are introduced in the following sections.

3. Genetic signatures potentially driving human cortical evolution

Because of a highly conserved repertoire of genes and protein structure among animals, the regulatory changes in gene expression have been proposed to be a strong driving force of phenotypic evolution (Carroll, 2003; King and Wilson, 1975; Shubin et al., 2009). Indeed many HS patterns of gene expression have been iden-

The diverse genetic mechanisms regulating the developmental processes related to the human cortical evolution are progres-

3.1. HS pattern of gene expression and their regulatory evolution

Please cite this article in press as: I.K. Suzuki, Molecular drivers of human cerebral cortical evolution. Neurosci. Res. (2019), https://doi.org/10.1016/j.neures.2019.05.007

G Model NSR-4289; No. of Pages 14

ARTICLE IN PRESS I.K. Suzuki / Neuroscience Research xxx (2019) xxx–xxx

5

Fig. 3. (A) Classifications of genes relevant to human cortical evolution. (B) Gene expression changes, such as those caused by mutations in cis regulatory elements. (C) Protein structure evolution caused by changes in splicing pattern (1) and by substitutions of amino acid residues (2). (D) Origination of new genes by a mechanism called “de novo genes” (1) and duplication (2).

tified from large-scale transcriptomics of developing human and primate cortices (Table 1) (Fig. 3B) (Ataman et al., 2016; Camp et al., 2015; Carri et al., 2013; Colantuoni et al., 2011; de la Torre-Ubieta et al., 2018; Fietz et al., 2012; Johnson et al., 2009, 2015; Kageyama et al., 2018; Kang et al., 2011; Kronenberg et al., 2018; Liu et al., 2017; McLean et al., 2011; Miller et al., 2014; Mora-Bermúdez et al., 2016; Nowakowski et al., 2017; Pollen et al., 2015, 2019; Sousa et al., 2017; Zhong et al., 2018; Zhu et al., 2018). These studies identified intriguing examples of HS molecular signatures regulating cortical development, for example, the higher level of PDGFD signaling is involved in the proliferation of human cortical RG progenitors, although it is not detected in the homologous RG progenitors of the mouse (Lui et al., 2014). Another interesting example is Osteocrin. This gene was identified in the screening of the genes upregulated by the neuronal activity specifically in the human but not in the mouse. This study revealed that Osteocrin gene has acquired enhancer elements during the primate evolution, which is bound and activated by the evolutionary conserved MEF2-family genes in an activity-dependent manner. Osteocrin functionally restricts the

receptive field size by eliminating dendritic arborization (Ataman et al., 2016). These examples highlight the importance of gene expression changes in the evolution of human cortical development. Evolutionary changes of gene expression are reasonably caused by the mutations in the genomic elements regulating expression. The comparative genomic and epigenomic approaches have been elucidating the regulatory mechanism of HS gene expression. The evolutionary conserved non-coding regions have been traditionally regarded as the candidates of regulatory elements, such as promoters and enhancers (Nobrega et al., 2003; Pennacchio et al., 2006; Shim et al., 2012; Visel et al., 2008, 2007), and therefore strong attention has been paid to HS changes in these conserved non-coding regions. Several independent studies identified phylogenetically conserved non-coding regions demonstrating human-specific changes as HAR; humanaccelerated region (Franchini and Pollard, 2015; Pollard et al., 2006b, 2006a), HANCS; human-accelerated conserved non-coding sequences (Doan et al., 2016; Prabhakar et al., 2008, 2006), and

Please cite this article in press as: I.K. Suzuki, Molecular drivers of human cerebral cortical evolution. Neurosci. Res. (2019), https://doi.org/10.1016/j.neures.2019.05.007

G Model

ARTICLE IN PRESS

NSR-4289; No. of Pages 14

I.K. Suzuki / Neuroscience Research xxx (2019) xxx–xxx

6

Table 1 Large-scale transcriptomic and epigenomic studies of human and primate cortical development. Transcriptome Study

Species

Sample

Stage

Method

Accession # in NCBI Gene Expression Omnibus (GEO) and notes

(Johnson et al., 2009) (Colantuoni et al., 2011) (Kang et al., 2011) (Fietz et al., 2012)

human human human human

GW18-24 2nd trimester-adult GW4-adult GW13-16

microarray microarray microarray bulk RNAseq

GSE13344 GSE30272 GSE25219 GSE38805

(Miller et al., 2014) (Lui et al., 2014)

human human

fetal cortical tissue fetal cortical tissue fetal cortical tissue fetal cortical tissue (VZ, iSVZ, oSVZ and CP) fetal cortical tissue fetal cortical tissue

GW15-21 GW14.5

Microarray & ISH bulk RNAseq

(Bae et al., 2014)

human

fetal cortical tissue

GW9

bulk RNAseq

(Johnson et al., 2015)

human

GW18-19

bulk RNAseq

(Pollen et al., 2015)

human human human

fetal cortical tissue (FACS LeX+, PROM1 + RG) fetal cortical tissue fetal cortical tissue organoid (prepared in the protocol (Lancaster and Knoblich, 2014)) culture of human fetal cortex

http://brainspan.org GSE62064; PDGFD signaling in human RG cell No available data; GPR56 GSE66217

GW16-18 GW12-13 33-65 DIV

scRNAseq scRNAseq scRNAseq

dbGaP: phs000989.v1.p1

GW17-20 + 15DIV

bulk RNAseq

GSE78688; Osteocrin shows an activity-dependent expression in human

GW11-13 <60 days

scRNAseq scRNAseq

<60 days

scRNAseq

GW16-17

scRNAseq

(Camp et al., 2015)

(Ataman et al., 2016)

(Mora-Bermúdez et al., 2016)

human

human human

chimpanzee

(Liu et al., 2017)

human

fetal cortical tissue organoid (prepared in the protocol (Lancaster and Knoblich, 2014)) organoid (prepared in the protocol (Lancaster and Knoblich, 2014)) fetal cortical tissue

(Nowakowski et al., 2017) (Suzuki et al., 2018)

human chimpanzee macaque human human

fetal cortical tissue fetal cortical tissue

21-40Y 23-30Y 7-11Y GW5-37 GW7-21

(Zhong et al., 2018) (Zhu et al., 2018)

human macaque

fetal cortical tissue fetal cortical tissue

GW8-23 64 gestational days-adult

(Pollen et al., 2019)

macaque human

fetal cortical tissue organoid (prepared in the protocol (Kadoshima et al., 2013)) organoid (prepared in the protocol (Kadoshima et al., 2013))

GW9-17 5-15 weeks

scRNAseq bulk RANseq & scRNAseq scRNAseq scRNAseq

5-15 weeks

scRNAseq

ChIP-Seq using H3K27ac and H3K4me2 antibodies Hi-C

(André M M Sousa et al., 2017)

chimpanzee

adult brain tissues

Epigenome (Reilly et al., 2015)

human

fetal cortical tissue

GW7-12

(Won et al., 2016)

human

GW17-18

(de la Torre-Ubieta et al., 2018)

human

fetal cortical tissue (GZ & CP) fetal cortical tissue (GZ & CP)

GW15-17

ANS; accelerated non-coding conserved sequences (Bird et al., 2007; Pollard et al., 2006a). Although there is a known example of HAR transcribed into a non-coding RNA specifically in the Cajal-Retizus neuron (Pollard et al., 2006b), most of these are validated to have the enhancer activity regulating the expression of neighboring genes during cortical development (Capra et al., 2013). One notable example is an enhancer of FZD8 gene, which shows significant sequence divergence between the human and the chim-

bulk RNAseq scRNAseq bulk RNAseq

bulk RNAseq + ATAC-seq

GSE75140

GSE86207

GSE90734; Primate-specific TMEM14B expands oSVZ progenitors NCBI BioProjects PRJNA236446 dbGaP: phs000989.v3 ArrayExpress: E-MTAB-6232; European Genome-phenome Archive: EGAD00001003915; Human-specific NOTCH2NL expands cortical neurogenesis. GSE104276 NCBI BioProjects PRJNA448973

GSE124299

GSE63649

GSE77565 dbGAP: phs001438; GEO: GSE95023

panzee (Boyd et al., 2015). The human-specific sequence of FZD8 enhancer drives an elevated level of expression in the mouse developing cortex than that of the chimpanzee, and the higher level of FZD8 increases progenitor cycling. In addition, the evolutionary conserved genomic regions specifically deleted in the human are also identified as hCONDELs (Kronenberg et al., 2018; McLean et al., 2011). hCONDELs were found in the genomic regions close to the genes relevant to brain development, such as Androgen recep-

Please cite this article in press as: I.K. Suzuki, Molecular drivers of human cerebral cortical evolution. Neurosci. Res. (2019), https://doi.org/10.1016/j.neures.2019.05.007

G Model NSR-4289; No. of Pages 14

ARTICLE IN PRESS I.K. Suzuki / Neuroscience Research xxx (2019) xxx–xxx

tor, GADD45 G, Wee1, and Cdc25C. Therefore, loss of these putative regulatory elements in the human evolution may have an impact on brain development through changing expression dynamics of these genes. Comparative genomics significantly contributed to the identification of HS regulatory elements relevant to human cortical evolution. More recently, regulatory elements are identified as the genomic regions marked by the epigenomic modifications, having a direct functional consequence of gene expression. The potential regulatory elements activated in the cortical progenitors and neurons in the human fetuses are comprehensively identified by chromatin immunoprecipitation and sequencing (ChIP-Seq) using the antibodies against specific histone modifications and transcriptional regulators (Reilly et al., 2015; Schmidt et al., 2010; Villar et al., 2015; Visel et al., 2009). Three-dimensional chromatin structure analyses also identified dynamic interactions of distal enhancers and promoters in the human cortical progenitors and neurons (Table 1) (de la Torre-Ubieta et al., 2018; Won et al., 2016). They identified a human-specific distal regulatory element, which binds to the promoter of FGFR2 only in the cortical progenitors but not in the differentiated neurons (de la Torre-Ubieta et al., 2018). This element is responsible for the expression of FGFR2 in the progenitors and the maintenance of progenitors from precocious neuronal differentiation. Taken together with comparative genomics and transcriptomics, these epigenomic data provide us a useful source of comprehensive information for investigating HS gene regulatory logic in cortical development. Lastly, the whole genome association study is also a powerful approach to identify genomic regions gene expression during corticogenesis. A notable example is the large-scale association study of the abnormalities of the brain structure and the genomic variations. This study utilizes clinical MRI (magnetic resonance imaging) images of more than 1000 individuals in combination with the genomic sequencing. This eventually identified a mutation related to a special type of abnormal cortical folding (Bae et al., 2014). The mutation was found in one of the promoters of GPR56, promoting cortical progenitor amplification, and then the reporter assay in mice showed that the mutant promoter drives less dosage of transcription than the wildtype form. Interestingly, compared to mice, human has acquired a larger number of alternative promoters of GPR56 and thus evolutionary changes of GPR56 expression may have a significant impact on cortical progenitor amplification.

7

lineage (Bond et al., 2002; Evans et al., 2006, 2004; Jayaraman et al., 2018; Kouprina et al., 2004; Mekel-bobrov et al., 2005; Montgomery et al., 2014, 2010; Xu et al., 2012; Zhang, 2003), suggesting that these proteins in the human have different biochemical properties from those in non-human animals. Consistently with this, the disease phenotype in the human is much more severe than those in the animal models (Jayaraman et al., 2018). Another well-known example of the positively selected gene is FOXP2. This gene was identified in the genetic study clarifying that the individuals who have a homozygous mutation on this gene have a severe disability in speech production without any other recognizable cognitive disabilities (Lai et al., 2001). Although there is an ongoing active discussion about the selective forces on FOXP2 in the human evolution (Atkinson et al., 2018; Fisher, 2019), molecular evolution studies identified that FOXP2 has two human-specific amino acid substitutions in comparison to that of chimpanzees (Enard et al., 2002; Zhang et al., 2002). Introduction of humanized FOXP2 in mice showed changes in “speech” pattern, emphasizing the biological significance of these amino acid substitutions of FOXP2 (Blass et al., 2009; French and Fisher, 2014; Reimers-Kipping et al., 2011; Schreiweis et al., 2014). The protein sequence evolution of corticogenesis-related genes and the SNPs (single nucleotide polymorphism) in coding sequences associated with the neurodevelopmental diseases will identify more genes potentially driving human cortical evolution. 3.3. HS gene repertory involved in cortical development Despite the deep phylogenetic conservation of a gene set, recent progress in comparative genomics have allowed identifying a significant number of HS genes that have appeared in recent human evolution. These HS genes are originated rarely through the “de novo” emergence (Fig. 3D1) (Ding et al., 2012; Long et al., 2013; Schlotterer, 2015; Tautz and Domazet-loˇso, 2011; Wu and Sharp, 2013), and primarily through the duplication of pre-existing genes by chromosomal rearrangements known as segmental duplications (Fig. 3D2) (Dennis et al., 2017; Dennis and Eichler, 2016; Dougherty et al., 2017; Kronenberg et al., 2018).

3.2.1. HS changes in alternative splicing pattern Among the genes expressing commonly during the human and non-human corticogenesis, some of their encoding proteins show the structural differences because of alternate choices of spliced exon (Fig. 3C1) (Barbosa-morais et al., 2012; Calarco et al., 2007; Johnson et al., 2009; Lin et al., 2010; Wang et al., 2015) and of amino acid substitutions (Fig. 3C2) (Dorus et al., 2004; Wang et al., 2006). Comparative study of splicing has been rapidly progressing owing to the recent advancement of RNA sequencing (Wang et al., 2015; Zhu et al., 2018). An interesting example of human-specific splicing pattern was found in NDE1 (Mosca et al., 2017), which is known to regulate cortical neurogenesis through its interaction with the centrosomal proteins (Feng and Walsh, 2004). More examples potentially causing HS cortical development will be identified from large-scale comparative splicing studies.

3.3.1. HS de novo transcripts and proteins Some of HS transcripts are originated de novo from non-genic genomic sequences, for example by an insertion of transcriptional promoter into the non-transcribed genomic region (Ruiz-Orera et al., 2015). In addition to de novo transcripts, HS de novo proteins have been reported, which are encoded in the transcripts whose orthologs in non-hominids are transcribed as non-protein coding RNAs without any reliable open reading frame (Chen et al., 2015; Knowles and Mclysaght, 2009; Li et al., 2010; Toll-riera et al., 2009; Wu et al., 2011; Xie et al., 2012). The mutational processes in the evolution create a protein-coding region in the phylogenetically conserved non-coding transcripts, and therefore the encoded protein is specific to the human or the hominids. Although it is still controversial how many such de novo transcripts and proteins do exist in the human genome, a significant number of human-specific de novo transcripts and proteins have been reported so far and some of them are genetically associated with the neuropsychiatry diseases (Knowles and Mclysaght, 2009; Li et al., 2010). None of these has been thoroughly studied in the context of brain development, it is worth investigating them as in the studies of HS genes originated by recent segmental duplication introduced in the next section.

3.2.2. HS evolution of protein sequence Protein evolution also has been studied in relation to brain evolution (Fig. 3C2). For example, the protein sequences encoded by the genes responsible for the primary microcephaly, such as ASPM and CDK5RAP2, are reported to be evolving rapidly in the human

3.3.2. HS genes originated by genomic segmental duplication Segmental duplications tend to occur in specific locations of the genome, becoming into the hot-spots of copy number variation (CNV) (Liu et al., 2012; Malhotra and Sebat, 2012; Sudmant et al., 2013). Interestingly, these CNV hot-spots are frequently

3.2. Evolution of the corticogenesis-related genes in protein level

Please cite this article in press as: I.K. Suzuki, Molecular drivers of human cerebral cortical evolution. Neurosci. Res. (2019), https://doi.org/10.1016/j.neures.2019.05.007

G Model NSR-4289; No. of Pages 14 8

ARTICLE IN PRESS I.K. Suzuki / Neuroscience Research xxx (2019) xxx–xxx

Fig. 4. (A) Protein structures of NOTCH2-family genes. Due to a number of nucleotide substitutions, protein structures of human-specific NOTCH2NL gene paralogs are different, in particular at their N-terminal signal peptide (yellow). (B) Human-specific NOTCH2NLB extends the period of cortical neurogenesis by upregulating Notch signaling in the progenitor cells and consequently increases the neuronal output.

associated with congenital neurodevelopmental and psychiatric diseases, suggesting that HS gene duplications may have impacts on brain development and function, and constitute another significant driver of brain evolution (Coe et al., 2012; Dennis and Eichler, 2016; Grayton et al., 2012; Kaminsky et al., 2011; Mefford and Eichler, 2009; Stankiewicz and Lupski, 2010; Sudmant et al., 2010; Weischenfeldt et al., 2013). This fits well with a traditional hypothesis that a phenotypic evolution is driven by gene duplication (Ohno, 1999, 1970). Indeed, recent studies identified that several gene duplications occurred in the human evolutionary lineage have pivotal functional impacts on cortical development (Fig. 3D2) (Charrier et al., 2012; Dennis et al., 2012; Fiddes et al., 2018; Florio et al., 2018, 2016, 2015; Fossati et al., 2016; Ju et al., 2016; Liu et al., 2017; Sporny et al., 2017; Suzuki et al., 2018), and the details for each duplicated gene are summarized elsewhere (Suzuki and Vanderhaeghen, 2019). A comprehensive transcriptome study of recently duplicated genes revealed that a significant number of HS genes are indeed expressed during human fetal corticogenesis (Suzuki et al., 2018). This screening identified 35 HS genes showing dynamic expression in the human developing cortex. In order to reveal the molecular mechanism regulating cortical expansion in human brain, potentially regulating the neurogenetic activity, are selected by overexpression assay in the mouse embryonic cortex. Eventually, this study successfully identified a sole candidate NOTCH2NLB and found that this gene indeed increases the number of cortical neurons (Fig. 4) (Suzuki et al., 2018). NOTCH2NLB (NOTCH2 N-terminal like B) is a sister gene of NOTCH2, displaying a copy number increase uniquely in the human (Duan et al., 2004; Fiddes et al., 2018; Florio et al., 2018; Suzuki et al., 2018). Modern and ancient human populations have four copies of human-specific NOTCH2NL genes (NOTCH2NLA, -B, -C and -R), all of which are conserved with the 5 part of NOTCH2 gene encoding N-terminal extracellular region of its protein, as well as a single copy of evolutionary conserved NOTCH2 (Fig. 4A). NOTCH2 and four NOTCH2NL genes show more than 99% identity in the nucleotide level, even in their intronic regions, suggesting a very recent duplication of these genes around 3–4 million years ago (Fiddes et al., 2018), consistently with the timing when the cranial volume of fossil humans had rapidly increased (Du et al., 2018). Even though NOTCH2NL genes are extremely similar to each other, they encode structurally different proteins because of the substitutions in the translation initiation sites and other amino acid residues (Fig. 4A). The expression of NOTCH2NL genes is highly enriched in the progenitors in the human fetal cortex. It

is noteworthy that they are expressed in the oSVZ in the second trimester as well as the consistent expression in the VZ through the developmental stages, suggesting that NOTCH2NL genes are functionally involved in the neurogenesis of multiple cortical progenitor subtypes. The clonal overexpression of NOTCH2NLB in a single human cortical RG progenitor, which is differentiated from the embryonic stem cell, demonstrates its role in expanding the number of progenies constituted by both the cycling progenitors and the postmitotic neurons (Fig. 4B). This is caused by cell autonomous upregulation of Notch signaling, and consequently leading to an extension of neurogenesis for a relatively long period. The precise molecular mechanism behind the regulation of Notch signaling is still under investigation, however, it was shown that NOTCH2NLB protein binds to and functionally suppresses a Notch ligand Delta like1 (DLL1) (Suzuki et al., 2018). In addition, careful investigations of the genomic sequences identified that either NOTCH2NLA or NOTCH2NLB, or both, are deleted or duplicated in the patients showing the abnormally smaller or larger cortical volume, respectively (1q21.1 microdeletion or microduplication syndromes)(Fiddes et al., 2018). This further strengthens the essential roles of NOTCH2NL genes in expanding cortical volume. Lastly, an expansion of GGC tri-nucleotide repeats in the upstream of NOTCH2NLC gene was recently found to be associated with a neurodegenerative disease (Sone et al., 2019), and this raises the possibility of future research approaching a relationship of HS genes and the diseases predominantly observed in the modern human population. In addition to NOTCH2NL, four more HS genes regulating corticogenesis have been identified so far. SRGAP2 is the first example of a gene duplication occurred exclusively in the human, which is functionally relevant to brain development and evolution (Charrier et al., 2012; Dennis et al., 2012). Among four copies of human SRGAP2 family genes, SRGAP2A shows a phylogenetically conserved structure and its mouse ortholog regulates neuronal morphology, migration, and connectivity in the developing cortex (Charrier et al., 2012; Fossati et al., 2016; Guerrier et al., 2009). Only N-terminal part of SRGAP2A is duplicated into three paralogs, SRGAP2B, -C, and -D, uniquely in the human. During corticogenesis, SRGAP2A and SRGAP2C are significantly expressed in the differentiated neurons. Due to the rapid accumulation of amino acid substitutions after the duplication, SRGAP2C has become less soluble compared to SRGAP2A and the predicted ancestral state of SRGAP2C. SRGAP2C can make a heterodimer with SRGAP2A through their F-BAR domain to decrease the solubility of SRGAP2A, and as a result downregulates the enzymatic activity of SRGAP2A

Please cite this article in press as: I.K. Suzuki, Molecular drivers of human cerebral cortical evolution. Neurosci. Res. (2019), https://doi.org/10.1016/j.neures.2019.05.007

G Model NSR-4289; No. of Pages 14

ARTICLE IN PRESS I.K. Suzuki / Neuroscience Research xxx (2019) xxx–xxx

(Sporny et al., 2017). In fact, experimental studies confirmed that human-specific SRGAP2C has a dominant negative effect on SRGAP2A in the cortical neurons (Charrier et al., 2012; Fossati et al., 2016). SRGAP2A accelerates the speed of radial migration and accelerates the maturation of both excitatory and inhibitory synapses in mice. Overexpression of SRGAP2C shows similar phenotypes caused by the loss-of-function of SRGAP2A. In other words, humanspecific SRGAP2C extend the period when the cortical neurons are in the immature state. Human is characterized by protracted maturation, i.e. the neoteny, which is thought to provide higher plasticity in the construction of neural circuit (Defelipe, 2011; Petanjek et al., 2011). Such human-specific protracted neuronal maturation is at least in part due to an evolutionary gain of SRGAP2C gene. Another example of the human-specific gene functionally involved in human corticogenesis is ARHGAP11B (Florio et al., 2016, 2015; Kalebic et al., 2018). ARHGAP11 family has two gene copies in the human, the evolutionary conserved ARHGAP11A and human-specific ARHGAP11B. Similar to NOTCH2 and SRGAP2, the human-specific paralog is originated by partial duplication of the ancestral gene and thereby ARHGAP11B encodes a truncated protein conserved with N terminal Rho GAP domain of ARHGAP11A. Interestingly, ARHGAP11B is not solely a shorter form of ARHGAP11A; ARHGAP11B protein does not appear to have Rho GAP enzymatic activity due to a point mutation causing a truncation of C terminal end of the domain by a frameshift afterward and surprisingly the loss of enzymatic activity is required for its functional participation in corticogenesis (Florio et al., 2016). Overexpression of ARHGAP11B in the mouse and ferret embryonic cortex induces an expansion of SVZ progenitors and, possibly because of that, leads to an increase in the degree of surface folding (Florio et al., 2016, 2015; Kalebic et al., 2018). These studies reveal an evolutionary impact of the emergence of ARHGAP11B on the expansion of the cortical surface area. The evolutionary timing of duplication is variable among the gene families. As mentioned above, the copy number of NOTCH2, SRGAP2, and ARHGAP11 are increased specifically in the human, suggesting that their duplications had occurred in the human lineage after the last common ancestor with the chimpanzee, however, two other examples, TBC1D3 and TMEM14B, are the gene families expanding during primate evolution. TBC1D3 is present only in the hominid species, and its copy number is amplified in the human (11 copies in GRCh38/hg38) (Hodzic et al., 2006). TBC1D3 protein contains TBC (Tre2-Bub2-Cdc16) domain, which has a Rab GAP activity regulating the intracellular vesicular transport of the membrane proteins such as an EGF receptor (Frittoli et al., 2008; Pei et al., 2002; Wainszelbaum et al., 2008). Overexpression of TBC1D3 in the mouse cortex leads to an increase of oRG-like cell and more complex folding of the cortical surface as in the overexpression of ARHGAP11B. Taken together with the loss-of-function in a human experimental model resulting in a decreased transition of progenitors from VZ to SVZ, it is likely that TBC1D3 enhances the conversion of RG cells into HOPX-expressing oRG cells by relaxing N-cadherin dependent adherence junction. The last example of gene duplication is primate-specific and rapidly evolving TMEM14B (Liu et al., 2017). Overexpression of TMEM14B in the mouse embryonic cortex induced more BP and oRG and the cortical surface became highly folded, similarly to overexpression of ARHGAP11B and TBC1D3. TMEM14B binds to and activates IQGAP1, which is an enhancer of cell cycle progression, and thus increase the proliferation of oSVZ progenitors. 4. Summary The genetic and cellular mechanisms behind the construction of HS features of the cerebral cortex is rapidly becoming elucidated, nevertheless, these must be the tips of icebergs and many more

9

mechanisms are expected to be identified. Furthermore, every single genetic mechanism found so far does not work solely but highly likely works in concert with one another. Therefore, the next important step is approaching the genetic interaction of multiple HS factors, in addition to further comprehensive search for novel genetic drivers. Acknowledgments The author thanks Pierre Vanderhaeghen, all members of Pierre Vanderhaeghen’s group in VIB KU Leuven, Kazuo Emoto and all members of Kazuo Emoto’s group at the University of Tokyo. The author is supported by the Leading Initiative for Excellent Young Researchers program of MEXT, Japan (#201890104). References Altman, J., Bayer, S.A., 2015. Development of the Human Neocortex -A Review and Interpretation of the Histological Record. Laboratory of Developmental Neurobiology, Inc. Arendt, D., 2008. The evolution of cell types in animals: emerging principles from molecular studies. Nat. Rev. Genet. 9, 868–882, http://dx.doi.org/10.1038/ nrg2416. Arendt, D., Musser, J.M., Baker, C.V.H., Bergman, A., Cepko, C., Erwin, D.H., Pavlicev, M., Schlosser, G., Widder, S., Laubichler, M.D., Wagner, G.P., 2016. The origin and evolution of cell types. Nat. Rev. Genet. 17, 744–757, http://dx.doi.org/10.1038/ nrg.2016.127. Ataman, B., Boulting, G.L., Harmin, D.A., Yang, M.G., Baker-Salisbury, M., Yap, E.L., Malik, A.N., Mei, K., Rubin, A.A., Spiegel, I., Durresi, E., Sharma, N., Hu, L.S., Pletikos, M., Griffith, E.C., Partlow, J.N., Stevens, C.R., Adli, M., Chahrour, M., Sestan, N., Walsh, C.A., Berezovskii, V.K., Livingstone, M.S., Greenberg, M.E., 2016. Evolution of Osteocrin as an activity-regulated factor in the primate brain. Nature 539, 242–247, http://dx.doi.org/10.1038/nature20111. Atkinson, E.G., Audesse, A.J., Palacios, J.A., Bobo, D.M., Webb, A.E., Ramachandran, S., Henn, B.M., 2018. No evidence for recent selection at FOXP2 among diverse human populations article no evidence for recent selection at FOXP2 among diverse human populations. Cell 174, http://dx.doi.org/10.1016/j.cell.2018.06. 048, 1424-1435.e15. Attardo, A., Calegari, F., Haubensak, W., Wilsch-Bräuninger, M., Huttner, W.B., B, W., 2008. Live imaging at the onset of cortical neurogenesis reveals differential appearance of the neuronal phenotype in apical versus basal progenitor progeny. PLoS One 3, e2388, http://dx.doi.org/10.1371/journal.pone.0002388. Bae, B.-I., Tietjen, I., Atabay, K.D., Evrony, G.D., Johnson, M.B., Asare, E., Wang, P.P., Murayama, A.Y., Im, K., Lisgo, S.N., Overman, L., et al., 2014. Evolutionarily dynamic alternative splicing of GPR56 regulates regional cerebral cortical patterning. Science (80-.) 343, 764–768, http://dx.doi.org/10.1126/ science.1244392. Barbosa-morais, N.L., Irimia, M., Pan, Q., Xiong, H.Y., Gueroussov, S., 2012. The evolutionary landscape of alternative splicing in vertebrate species. Science (80-.) 338, 1587–1594. Bayer, S.A., Altman, J., Russo, R.J., Zhang, X., 1993. Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat. Neurotoxicology 14, 83–144. Belgard, T.G., Montiel, J.F., 2013. Things change: how comparative transcriptomics suggest the pallium has evolved at multiple levels of organization. Brain Behav. Evol. 82, 150–152, http://dx.doi.org/10.1159/000354969. Belgard, T.G., Montiel, J.F., Wang, W.Z., García-Moreno, F., Margulies, E.H., Ponting, C.P., Molnár, Z., 2013. Adult pallium transcriptomes surprise in not reflecting predicted homologies across diverse chicken and mouse pallial sectors. Proc. Natl. Acad. Sci. U. S. A. 110, 13150–13155, http://dx.doi.org/10.1073/pnas. 1307444110. Betizeau, M., Cortay, V., Patti, D., Pfister, S., Gautier, E., Bellemin-Ménard, A., Afanassieff, M., Huissoud, C., Douglas, R.J., Kennedy, H., Dehay, C., 2013. Precursor diversity and complexity of lineage relationships in the outer subventricular zone of the primate. Neuron 80, 442–457, http://dx.doi.org/10.1016/j.neuron. 2013.09.032. Bird, C.P., Stranger, B.E., Liu, M., Thomas, D.J., Ingle, C.E., Beazley, C., Miller, W., Hurles, M.E., Dermitzakis, E.T., 2007. Fast-evolving noncoding sequences in the human genome. Genome Biol. 8, R118, http://dx.doi.org/10.1186/gb-2007-8-6-r118. Blass, T., Somel, M., Enard, W., Gehre, S., Hammerschmidt, K., Ho, S.M., Schreiweis, C., Winter, C., Sohr, R., Becker, L., Wiebe, V., et al., 2009. A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice. Cell 137, 961–971, http:// dx.doi.org/10.1016/j.cell.2009.03.041. Bond, J., Roberts, E., Mochida, G.H., Hampshire, D.J., Scott, S., Askham, J.M., Springell, K., Mahadevan, M., Crow, Y.J., Markham, A.F., Walsh, C., et al., 2002. ASPM is a major determinant of cerebral cortical size. Nat. Genet. 32, 316–320, http://dx. doi.org/10.1038/ng995. Boyd, J.L., Skove, S.L., Rouanet, J.P., Pilaz, L.-J., Bepler, T., Gordân, R., Wray, Ga., Silver, D.L., 2015. Human-chimpanzee differences in a FZD8 enhancer alter cell-cycle dynamics in the developing neocortex. Curr. Biol., 1–8, http://dx.doi.org/10. 1016/j.cub.2015.01.041.

Please cite this article in press as: I.K. Suzuki, Molecular drivers of human cerebral cortical evolution. Neurosci. Res. (2019), https://doi.org/10.1016/j.neures.2019.05.007

G Model NSR-4289; No. of Pages 14 10

ARTICLE IN PRESS I.K. Suzuki / Neuroscience Research xxx (2019) xxx–xxx

Briscoe, S.D., Albertin, C.B., Rowell, J.J., Ragsdale, C.W., Briscoe, S.D., Albertin, C.B., Rowell, J.J., Ragsdale, C.W., 2018. Neocortical association cell types in the forebrain of birds and alligators article neocortical association cell types in the forebrain of birds and alligators. Curr. Biol., 1–11, http://dx.doi.org/10.1016/j. cub.2018.01.036. Briscoe, S.D., Ragsdale, C.W., 2018. Homology, neocortex, and the evolution of developmental mechanisms. Science (80-.) 362, 190–193. Cahalane, D.J., Charvet, C.J., Finlay, B.L., 2014. Modeling local and cross-species neuron number variations in the cerebral cortex as arising from a common mechanism. Proc. Natl. Acad. Sci. U. S. A., 201409271, http://dx.doi.org/10.1073/ pnas.1409271111. Calarco, J.A., Xing, Y., Cáceres, M., Calarco, J.P., Xiao, X., Pan, Q., Lee, C., Preuss, T.M., Blencowe, B.J., 2007. Global analysis of alternative splicing differences between humans and chimpanzees. Genes Dev. 21, 2963–2975, http://dx.doi. org/10.1101/gad.1606907.noncoding. Camp, J.G., Badsha, F., Florio, M., Kanton, S., Gerber, T., Wilsch-Bräuninger, M., Lewitus, E., Sykes, A., Hevers, W., Lancaster, M., Knoblich, J.A., et al., 2015. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc. Natl. Acad. Sci. 112, 15672–15677, http://dx.doi.org/10. 1073/pnas.1520760112. Capra, J.A., Erwin, G.D., Mckinsey, G., Rubenstein, J.L.R., Pollard, K.S., Pollard, K.S., 2013. Many human accelerated regions are developmental enhancers. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 368, 20130025. Cárdenas, A., Villalba, A., de Juan Romero, C., Picó, E., Kyrousi, C., Tzika, A.C., TessierLavigne, M., Ma, L., Drukker, M., Cappello, S., Borrell, V., 2018. Evolution of cortical neurogenesis in amniotes controlled by robo signaling levels. Cell 174, http:// dx.doi.org/10.1016/j.cell.2018.06.007, 590-606.e21. Carri, A.D., Onorati, M., Lelos, M.J., Castiglioni, V., Faedo, A., Menon, R., Camnasio, S., Vuono, R., Spaiardi, P., Talpo, F., Toselli, M., et al., 2013. Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32+ medium-sized spiny neurons. Development 140, 301–312, http://dx.doi.org/10.1242/dev.084608. Carroll, S.B., 2003. Genetics and the making of Homo sapiens. Nature 422, 849–857, http://dx.doi.org/10.1038/nature01495. Charrier, C., Joshi, K., Coutinho-Budd, J., Kim, J.-E., Lambert, N., de Marchena, J., Jin, W.-L., Vanderhaeghen, P., Ghosh, A., Sassa, T., Polleux, F., 2012. Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation. Cell 149, 923–935, http://dx.doi.org/10.1016/j.cell.2012.03.034. Chen, C.-C., Winkler, C.M., Pfenning, A.R., Jarvis, E.D., 2013. Molecular profiling of the developing avian telencephalon: regional timing and brain subdivision continuities. J. Comp. Neurol. 521, 3666–3701, http://dx.doi.org/10.1002/cne.23406. Chen, J., Shen, Q.S., Zhou, W., Peng, J., He, B.Z., 2015. Emergence, retention and selection: a trilogy of origination for functional de novo proteins from ancestral lncrnas in primates. PLoS Genet. 11, e1005391, http://dx.doi.org/10.1371/ journal.pgen.1005391. Chenn, A., Walsh, C.A., 2002. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science (80-.) 297, 365–370. Clancy, B., Darlington, R., Finlay, B., 2001. Translating developmental time across mammalian species. Neuroscience 105, 7–17. Coe, B.P., Girirajan, S., Eichler, E.E., 2012. The genetic variability and commonality of neurodevelopmental disease. Am. J. Med. Genet. Part C Semin. Med. Genet. 160C, 118–129, http://dx.doi.org/10.1002/ajmg.c.31327. Colantuoni, C., Lipska, B.K., Ye, T., Hyde, T.M., Tao, R., Leek, J.T., Colantuoni, Ea., Elkahloun, A.G., Herman, M.M., Weinberger, D.R., Kleinman, J.E., 2011. Temporal dynamics and genetic control of transcription in the human prefrontal cortex. Nature 478, 519–523, http://dx.doi.org/10.1038/nature10524. de la Torre-Ubieta, L., Stein, J.L., Won, H., Opland, C.K., Liang, D., Lu, D., Geschwind, D.H., 2018. The dynamic landscape of open chromatin during human cortical neurogenesis. Cell 172, http://dx.doi.org/10.1016/j.cell.2017.12.014, 289-304 e18. Defelipe, J., 2011. The evolution of the brain, the human nature of cortical circuits, and intellectual creativity. Front. Neuroanat. 5, 29, http://dx.doi.org/10.3389/ fnana.2011.00029. Dehay, C., Kennedy, H., Kosik, K.S., Lyon, I., Lyon, D., 2015. The outer subventricular zone and primate-specific cortical complexification. Neuron 85, 683–694, http:// dx.doi.org/10.1016/j.neuron.2014.12.060. Dennis, M.Y., Eichler, E.E., 2016. Human adaptation and evolution by segmental duplication. Curr. Opin. Genet. Dev. 41, 44–52, http://dx.doi.org/10.1016/j.gde. 2016.08.001. Dennis, M.Y., Harshman, L., Nelson, B.J., Penn, O., Cantsilieris, S., Huddleston, J., Antonacci, F., Penewit, K., Denman, L., Raja, A., Baker, C., et al., 2017. The evolution and population diversity of human-specific segmental duplications. Nat. Ecol. Evol. 1, 69, http://dx.doi.org/10.1038/s41559-016-0069. Dennis, M.Y., Nuttle, X., Sudmant, P.H., Antonacci, F., Graves, T.A., Nefedov, M., Rosenfeld, J.A., Sajjadian, S., Malig, M., Kotkiewicz, H., Curry, C.J., et al., 2012. Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication. Cell 149, 912–922, http://dx.doi.org/10.1016/j.cell.2012.03.033. Desai, A.R., McConnell, S.K., 2000. Progressive restriction in fate potential by neural progenitors during cerebral cortical development. Development 127, 2863–2872. Ding, Y., Zhou, Q., Wang, W., 2012. Origins of new genes and evolution of their novel functions. Annu. Rev. Ecol. Evol. Syst. 43, 345–363, http://dx.doi.org/10.1146/ annurev-ecolsys-110411-160513. Doan, R.N., Bae, B.-I., Cubelos, B., Chang, C., Hossain, A.A., Al-Saad, S., Mukaddes, N.M., Oner, O., Al-Saffar, M., Balkhy, S., Gascon, G.G., et al., 2016. Mutations in human

accelerated regions disrupt cognition and social behavior. Cell 167, http://dx. doi.org/10.1016/j.cell.2016.08.071, 341-354.e12. Dorus, S., Vallender, E.J., Evans, P.D., Anderson, J.R., Gilbert, S.L., Mahowald, M., Wyckoff, G.J., Malcom, C.M., Lahn, B.T., 2004. Accelerated evolution of nervous system genes in the origin of Homo sapiens. Cell 119, 1027–1040. Dougherty, M.L., Nuttle, X., Penn, O., Nelson, B.J., Huddleston, J., Baker, C., Harshman, L., Duyzend, M.H., Ventura, M., Antonacci, F., Sandstrom, R., et al., 2017. The birth of a human-specific neural gene by incomplete duplication and gene fusion. Genome Biol. 18, 49, http://dx.doi.org/10.1186/s13059-017-11639. Du, A., Zipkin, A.M., Hatala, K.G., Renner, E., Baker, J.L., Bianchi, S., Bernal, K.H., Wood, B.A., Du, A., 2018. Pattern and process in hominin brain size evolution are scaledependent. Proc. R. Soc. B 285, 20172738. Duan, Z., Li, F.-Q., Wechsler, J., Meade-White, K., Williams, K., Benson, K.F., Horwitz, M., 2004. A novel notch protein, N2N, targeted by neutrophil elastase and implicated in hereditary neutropenia. Mol. Cell. Biol. 24, 58–70, http://dx.doi.org/10. 1128/MCB.24.1.58-70.2004. Dugas-Ford, J., Rowell, J.J., Ragsdale, C.W., 2012. Cell-type homologies and the origins of the neocortex. Proc. Natl. Acad. Sci. U. S. A. 109, 16974–16979, http://dx.doi. org/10.1073/pnas.1204773109. Enard, W., Przeworski, M., Fisher, S.E., Lai, C.S.L., 2002. Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418, 869–872. Evans, P.D., Anderson, J.R., Vallender, E.J., Gilbert, S.L., Malcom, C.M., Dorus, S., Lahn, B.T., 2004. Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans. Hum. Mol. Genet. 13, 489–494, http://dx.doi.org/10.1093/hmg/ ddh055. Evans, P.D., Vallender, E.J., Lahn, B.T., 2006. Molecular evolution of the brain size regulator genes CDK5RAP2 and CENPJ. Gene 375, 75–79, http://dx.doi.org/10. 1016/j.gene.2006.02.019. Feng, Y., Walsh, C.A., 2004. Mitotic spindle regulation by Nde1 controls cerebral cortical size. Neuron 44, 279–293, http://dx.doi.org/10.1016/j.neuron.2004.09. 023. Fiddes, I.T., Lodewijk, G.A., Mooring, M., Bosworth, C.M., Ewing, A.D., Mantalas, G.L., Novak, A.M., van den Bout, A., Bishara, A., Rosenkrantz, J.L., Lorig-Roach, R., et al., 2018. Human-specific NOTCH2NL genes affect notch signaling and cortical neurogenesis. Cell 173, 1356–1369, http://dx.doi.org/10.1016/j.cell.2018. 03.051. Fietz, Sa., Lachmann, R., Brandl, H., Kircher, M., Samusik, N., Schroder, R., Lakshmanaperumal, N., Henry, I., Vogt, J., Riehn, a., Distler, W., et al., 2012. Transcriptomes of germinal zones of human and mouse fetal neocortex suggest a role of extracellular matrix in progenitor self-renewal. Proc. Natl. Acad. Sci. U. S. A. 109, 11836–11841, http://dx.doi.org/10.1073/pnas.1209647109. Fietz, S.A., Kelava, I., Vogt, J., Wilsch-Bräuninger, M., Stenzel, D., Fish, J.L., Corbeil, D., Riehn, A., Distler, W., Nitsch, R., Huttner, W.B., 2010. OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling. Nat. Neurosci. 13, 690–699, http://dx.doi.org/10.1038/nn.2553. Fisher, S.E., 2019. Human genetics: the evolving story of FOXP2. Curr. Biol. 29, R65–R67, http://dx.doi.org/10.1016/j.cub.2018.11.047. Florio, M., Albert, M., Taverna, E., Namba, T., Brandl, H., Lewitus, E., Haffner, C., Sykes, A., Wong, F.K., Peters, J., Guhr, E., et al., 2015. Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion. Science (80.) 347, 1465–1470. Florio, M., Heide, M., Pinson, A., Brandl, H., Albert, M., Winkler, S., Wimberger, P., Huttner, W.B., Hiller, M., Carus, G., Universita, T., 2018. Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex. Elife 7, e32332. Florio, M., Namba, T., Pa a bo, S., Hiller, M., Huttner, W.B., 2016. A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification. Sci. Adv. 2, e1601941, http://dx.doi.org/10.1126/sciadv.1601941. Fossati, M., Pizzarelli, R., Schmidt, E.R., Kupferman, J.V., Stroebel, D., Polleux, F., Charrier, C., 2016. SRGAP2 and its human-specific paralog co-regulate the development of excitatory and inhibitory synapses. Neuron 91, 356–369, http://dx. doi.org/10.1016/j.neuron.2016.06.013. Franchini, L.F., Pollard, K.S., 2015. Can a few non-coding mutations make a human brain? BioEssays, http://dx.doi.org/10.1002/bies.201500049, n/a-n/a. French, C.A., Fisher, S.E., 2014. What can mice tell us about Foxp2 function? Curr. Opin. Neurobiol. 28C, 72–79, http://dx.doi.org/10.1016/j.conb.2014.07.003. Frittoli, E., Palamidessi, A., Pizzigoni, A., Lanzetti, L., Garre, M., Troglio, F., Troilo, A., Fukuda, M., Paolo, P., Fiore, D., Scita, G., Confalonieri, S., 2008. The primatespecific protein TBC1D3 is required for optimal macropinocytosis in a novel ARF6-dependent pathway. Mol. Biol. Cell 19, 1304–1316, http://dx.doi.org/10. 1091/mbc.E07. Gao, P., Postiglione, M.P., Krieger, T.G., Hernandez, L., Wang, C., Han, Z., Streicher, C., Papusheva, E., Insolera, R., Chugh, K., Kodish, O., et al., 2014. Deterministic progenitor behavior and unitary production of neurons in the neocortex. Cell 159, 775–788, http://dx.doi.org/10.1016/j.cell.2014.10.027. Garcıa-Moreno, F., Vasistha, N.A., Trevia, N., Bourne, J.A., García-Moreno, F., Molnár, Z., 2012. Compartmentalization of cerebral cortical germinal zones in a lissencephalic primate and gyrencephalic rodent. Cereb. Cortex 22, 482–492, http://dx.doi.org/10.1093/cercor/bhr312. Geschwind, D.H., Rakic, P., 2013. Cortical evolution: judge the brain by its cover. Neuron 80, 633–647, http://dx.doi.org/10.1016/j.neuron.2013.10.045. Grayton, H.M., Fernandes, C., Rujescu, D., Collier, D.A., 2012. Copy number variations in neurodevelopmental disorders. Prog. Neurobiol. 99, 81–91, http://dx.doi.org/ 10.1016/j.pneurobio.2012.07.005.

Please cite this article in press as: I.K. Suzuki, Molecular drivers of human cerebral cortical evolution. Neurosci. Res. (2019), https://doi.org/10.1016/j.neures.2019.05.007

G Model NSR-4289; No. of Pages 14

ARTICLE IN PRESS I.K. Suzuki / Neuroscience Research xxx (2019) xxx–xxx

Greig, L.C., Woodworth, M.B., Galazo, M.J., Padmanabhan, H., Macklis, J.D., 2013. Molecular logic of neocortical projection neuron specification, development and diversity. Nat. Rev. Neurosci. 14, 755–769, http://dx.doi.org/10.1038/nrn3586. Guerrier, S., Coutinho-Budd, J., Sassa, T., Gresset, A., Jordan, N.V., Chen, K., Jin, W.-L., Frost, A., Polleux, F., 2009. The F-BAR domain of srGAP2 induces membrane protrusions required for neuronal migration and morphogenesis. Cell 138, 990–1004, http://dx.doi.org/10.1016/j.cell.2009.06.047. Hansen, D.V., Lui, J.H., Parker, P.R.L., Kriegstein, A.R., 2010. Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464, 554–561, http:// dx.doi.org/10.1038/nature08845. Hassiotis, M., Ashwell, K.W.S., 2003. Neuronal classes in the isocortex of a monotreme, the Australian echidna (Tachyglossus aculeatus). Brain Behav. Evol. 61, 6–27, http://dx.doi.org/10.1159/000068877. Hassiotis, M., Paxinos, G., Ashwell, K.W.S., 2005. Cyto- and chemoarchitecture of the cerebral cortex of an echidna (Tachyglossus aculeatus). II. Laminar organization and synaptic density. J. Comp. Neurol. 482, 94–122, http://dx.doi.org/10.1002/ cne.20353. Hatakeyama, J., Sato, H., Shimamura, K., 2017. Developing Guinea Pig Brain as a Model for Cortical Folding., pp. 286–301, http://dx.doi.org/10.1111/dgd.12371. Haubensak, W., Attardo, A., Denk, W., Huttner, W.B., 2006. Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. Proc. Natl. Acad. Sci. U. S. A. 101, 3196–3201, http://dx.doi.org/10. 1073/pnas.0308600100. Herculano-Houzel, S., 2017. Numbers of neurons as biological correlates of cognitive capability. Curr. Opin. Behav. Sci. 16, 1–7, http://dx.doi.org/10.1016/j.cobeha. 2017.02.004. Herculano-Houzel, S., 2009. The human brain in numbers: a linearly scaled-up primate brain. Front. Hum. Neurosci. 3, 1–11, http://dx.doi.org/10.3389/neuro.09. 031.2009. Hill, R.S., Walsh, C.A., 2005. Molecular insights into human brain evolution. Nature 437, 13–16, http://dx.doi.org/10.1038/nature04103. Hirabayashi, Y., Gotoh, Y., 2010. Epigenetic control of neural precursor cell fate during development. Nat. Rev. Neurosci. 11, 377–388, http://dx.doi.org/10.1038/ nrn2810. Hodzic, D., Kong, C., Wainszelbaum, M.J., Charron, A.J., Su, X., Stahl, P.D., 2006. TBC1D3, a hominoid oncoprotein, is encoded by a cluster of paralogues located on chromosome 17q12. Genomics 88, 731–736, http://dx.doi.org/10.1016/j. ygeno.2006.05.009. Hubel, D.H., Wiesel, T.N., 1969. Anatomical demonstration of columns in the monkey striate cortex. Nature 221, 747–750. Hubel, D.H., Wiesel, T.N., 1963. Shape and arrangement of columns in cat’s striate cortex. J. Physiol. 165, 559–568. Huttner, W.B., Kelava, I., Lewitus, E., 2013. Progenitor networking in the fetal primate neocortex. Neuron 80, 259–262, http://dx.doi.org/10.1016/j.neuron.2013. 10.004. Jacobi, A.A., Naumann, R.K., Laurent, G., Tushev, G., Tosches, M.A., Yamawaki, T.M., 2018. Evolution of pallium, hippocampus, and cortical cell types revealed by single-cell transcriptomics in reptiles. Science (80-.) 360, 881–888, http://dx. doi.org/10.1126/science.aar4237. Jarvis, E.D., Gunturkun, O., Bruce, L., Csillag, A.A., Karten, H.J., Kuenzel, W., Medina, L., Paxinos, G., Perkel, D.J., Shimizu, T., Striedter, G., et al., 2005. Avian brains and a new understanding of vertebrate brain evolution. Nat. Rev. Neurosci. 6, 151–159, http://dx.doi.org/10.1038/nrn1606. Jarvis, E.D., Yu, J., Rivas, M.V., Horita, H., Feenders, G., Whitney, O., Jarvis, S.C., Kubikova, L., Puck, A.E.P., Siang-bakshi, C., Martin, S., et al., 2013. Global view of the functional molecular organization of the avian cerebrum: mirror images and functional columns. J. Comp. Neurol. 521, 3614–3665, http://dx.doi.org/10. 1002/cne.23404. Jayaraman, D., Bae, B.-I., Walsh, C.A., 2018. The genetics of primary microcephaly. Annu. Rev. Genomics Hum. Genet. 19, 177–200, http://dx.doi.org/10.1146/ annurev-genom-083117-021441. ´ D., Johnson, M.B., Kawasawa, Y.I., Mason, C.E., Krsnik, Z., Coppola, G., Bogdanovic, Geschwind, D.H., Mane, S.M., State, M.W., Sestan, N., 2009. Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron 62, 494–509, http://dx.doi.org/10.1016/j.neuron.2009.03.027. Johnson, M.B., Wang, P.P., Atabay, K.D., Murphy, E.A., Doan, R.N., Hecht, J.L., Walsh, C., 2015. Single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex. Nat. Neurosci., 6–8, http://dx.doi.org/10.1038/nn. 3980. Ju, X.C., Hou, Q.Q., Sheng, A.L., Wu, K.Y., Zhou, Y., Jin, Y., Wen, T., Yang, Z., Wang, X., Luo, Z.G., 2016. The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice. Elife 5, 1–25, http://dx.doi.org/10.7554/eLife.18197. Kaas, J.H., 2011. Neocortex in early mammals and its subsequent variations. Ann. N. Y. Acad. Sci. 1225, 28–36, http://dx.doi.org/10.1111/j.1749-6632.2011.05981.x. Kadoshima, T., Sakaguchi, H., Nakano, T., Soen, M., Ando, S., Eiraku, M., Sasai, Y., 2013. Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex. Proc. Natl. Acad. Sci. U. S. A. 110, 20284–20289, http://dx.doi.org/10.1073/pnas.1315710110. Kageyama, J., Wollny, D., Treutlein, B., Camp, J.G., 2018. ShinyCortex: exploring single-cell transcriptome data from the developing human cortex. Front. Neurosci. 12, 315, http://dx.doi.org/10.3389/fnins.2018.00315. Kageyama, R., Shimojo, H., Ohtsuka, T., 2019. Dynamic control of neural stem cells by bHLH factors. Neurosci. Res. 138, 12–18, http://dx.doi.org/10.1016/j.neures. 2018.09.005.

11

Kalebic, N., Gilardi, C., Albert, M., Gilardi, C., Namba, T., Long, K.R., Kostic, M., Langen, B., Huttner, W.B., 2018. Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex. Elife 7, e41241, http://dx. doi.org/10.7554/elife.41241. Kalebic, N., Gilardi, C., Stepien, B., Wilsch-Bräuninger, M., Long, K.R., Namba, T., Florio, M., Langen, B., Lombardot, B., Shevchenko, A., Kilimann, M.W., et al., 2019. Neocortical expansion due to increased proliferation of basal progenitors is linked to changes in their morphology. Cell Stem Cell, 1–16, http://dx.doi.org/10.1016/ J.STEM.2019.02.017. Kaminsky, E.B., Kaul, V., Paschall, J., Church, D.M., Bunke, B., Kunig, D., Moreno-DeLuca, D., Moreno-De-Luca, A., Mulle, J.G., Warren, S.T., Richard, G., et al., 2011. An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. Genet. Med. 13, 777–784, http://dx.doi.org/10.1097/GIM.0b013e31822c79f9. Kang, H.J., Kawasawa, Y.I., Cheng, F., Zhu, Y., Xu, X., Li, M., Sousa, A.M.M., Pletikos, M., Meyer, Ka., Sedmak, G., Guennel, T., et al., 2011. Spatio-temporal transcriptome of the human brain. Nature 478, 483–489, http://dx.doi.org/10.1038/ nature10523. Katz, L.C., Crowley, J.C., 2002. Development of cortical circuits: lessons from ocular dominance columns. Nat. Rev. Neurosci. 3, 34–42, http://dx.doi.org/10.1038/ nrn703. Kawaguchi, A., 2019. Temporal patterning of neocortical progenitor cells: how do they know the right time? Neurosci. Res. 138, 3–11, http://dx.doi.org/10.1016/ j.neures.2018.09.004. Kelava, I., Lewitus, E., Huttner, W.B., 2013. The secondary loss of gyrencephaly as an example of evolutionary phenotypical reversal. Front. Neuroanat. 7, 16, http:// dx.doi.org/10.3389/fnana.2013.00016. King, M.-C., Wilson, A.C., 1975. Evolution at two levels in humans and chimpanzees. Science (80-.) 188, 107–116. Knowles, D.G., Mclysaght, A., 2009. Recent de novo origin of human protein-coding genes. Genome Res. 19, 1752–1759, http://dx.doi.org/10.1101/gr.095026.109. 19. Kostic, M., Paridaen, J.T., Long, K.R., Kalebic, N., Langen, B., Grübling, N., Wimberger, P., Kawasaki, H., Namba, T., Huttner, W.B., 2019. YAP activity is necessary and sufficient for basal progenitor abundance and proliferation in the developing neocortex. Cell Rep. 27, 1103–1118, http://dx.doi.org/10.1016/j.celrep.2019.03. 091. Kouprina, N., Pavlicek, A., Mochida, G.H., Solomon, G., Gersch, W., Yoon, Y., Collura, R., Ruvolo, M., Barrett, J.C., Woods, C.G., Walsh, C.A., Jurka, J., Larionov, V., 2004. Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion. PLoS Biol. 2, 653–663, http://dx.doi.org/10.1371/ journal.pbio.0020126. Kowalczyk, T., Pontious, A., Englund, C., Daza, R.A.M., Bedogni, F., Hodge, R., Attardo, A., Bell, C., Huttner, W.B., Hevner, F., 2009. Intermediate neuronal progenitors (basal progenitors) produce pyramidal– projection neurons for all layers of cerebral cortex. Cereb. Cortex 19, 2439–2450, http://dx.doi.org/10.1093/cercor/ bhn260. Kronenberg, Z.N., Fiddes, I.T., Gordon, D., Murali, S., Cantsilieris, S., Meyerson, O.S., Underwood, J.G., Nelson, B.J., Chaisson, M.J.P., Dougherty, M.L., Munson, K.M., et al., 2018. High-resolution comparative analysis of great ape genomes. Science (80-.) 360, http://dx.doi.org/10.1126/science.aar6343, eaar6343. Krubitzer, L., 2007. The magnificent compromise: cortical field evolution in mammals. Neuron 56, 201–208, http://dx.doi.org/10.1016/j.neuron.2007.10.002. Lai, C.S.L., Fisher, S.E., Hurst, J.A., Vargha-khadem, F., 2001. A forkhead-domain gene is mutated in a severe speech and language disorder. Nature 413, 519–523. Lancaster, M., Knoblich, J., 2014. Generation of cerebral organoids from human pluripotent stem cells. Nat. Protoc. 9, 2329–2340, http://dx.doi.org/10.1038/ nprot.2014.158. Lein, E.S., Belgard, T.G., Hawrylycz, M., Molnar, Z., 2017. Transcriptomic perspectives on neocortical structure, development, evolution, and disease. Annu. Rev. Neurosci. 40, 629–652, http://dx.doi.org/10.1146/annurev-. Leone, D.P., Srinivasan, K., Chen, B., Alcamo, E., Mcconnell, S.K., 2008. The determination of projection neuron identity in the developing cerebral cortex. Curr. Opin. Neurobiol. 18, 28–35, http://dx.doi.org/10.1016/j.conb.2008.05.006. Lewitus, E., Kelava, I., Kalinka, A.T., Tomancak, P., Huttner, W.B., 2014. An adaptive threshold in mammalian neocortical evolution. PLoS Biol. 12, e1002000, http:// dx.doi.org/10.1371/journal.pbio.1002000. Li, C., Zhang, Yong, Wang, Z., Zhang, Yan, Cao, C., Zhang, P., Li, X., Yu, Q., Zheng, X., Du, Q., Uhl, G.R., Liu, Q., Wei, L., 2010. A human-specific de novo protein-coding gene associated with human brain functions. PLoS Comput. Biol. 6, e1000734, http://dx.doi.org/10.1371/journal.pcbi.1000734. Lin, L., Shen, S., Jiang, P., Sato, S., Davidson, B.L., Xing, Y., 2010. Evolution of alternative splicing in primate brain transcriptomes. Hum. Mol. Genet. 19, 2958–2973, http://dx.doi.org/10.1093/hmg/ddq201. Liu, J., Liu, W., Yang, L., Wu, Q., Zhang, H., Fang, A., Li, L., Xu, X., Sun, L., Zhang, J., Tang, F., Wang, X., 2017. The primate-specific gene TMEM14B marks outer radial glia cells and promotes cortical expansion and folding article the primate-specific gene TMEM14B marks outer radial glia cells and promotes cortical expansion and folding. Cell Stem Cell 21, 635–649, http://dx.doi.org/10.1016/j.stem.2017. 08.013. Liu, P., Carvalho, C.M.B., Hastings, P.J., Lupski, J.R., 2012. Mechanisms for recurrent and complex human genomic rearrangements. Curr. Opin. Genet. Dev. 22, 211–220, http://dx.doi.org/10.1016/j.gde.2012.02.012. Long, M., Vankuren, N.W., Chen, S., Vibranovski, M.D., 2013. New gene evolution: little did we know. Annu. Rev. Genetics 47, 307–333, http://dx.doi.org/10.1146/ annurev-genet-111212-133301.

Please cite this article in press as: I.K. Suzuki, Molecular drivers of human cerebral cortical evolution. Neurosci. Res. (2019), https://doi.org/10.1016/j.neures.2019.05.007

G Model NSR-4289; No. of Pages 14 12

ARTICLE IN PRESS I.K. Suzuki / Neuroscience Research xxx (2019) xxx–xxx

Long, K.R., Newland, B., Florio, M., Kalebic, N., Langen, B., Kolterer, A., Wimberger, P., Huttner, W.B., 2018. Extracellular matrix components HAPLN1, lumican, and collagen I cause hyaluronic acid-dependent folding of the developing human neocortex. Neuron 99, 702–719, http://dx.doi.org/10.1016/j.neuron.2018.07. 013. Lui, J.H., Hansen, D.V., Kriegstein, A.R., 2011. Development and evolution of the human neocortex. Cell 146, 18–36, http://dx.doi.org/10.1016/j.cell.2011.06.030. Lui, J.H., Nowakowski, T.J., Pollen, A.A., Javaherian, A., Kriegstein, A.R., Oldham, M.C., 2014. Radial glia require PDGFD–PDGFR␤ signalling in human but not mouse neocortex. Nature 515, 264–268, http://dx.doi.org/10.1038/nature13973. Malhotra, D., Sebat, J., 2012. CNVs: harbingers of a rare variant revolution in psychiatric genetics. Cell 148, 1223–1241, http://dx.doi.org/10.1016/j.cell.2012.02. 039. Marioni, J.C., Arendt, D., 2017. How single-cell genomics is changing evolutionary and developmental biology. Annu. Rev. Cell Dev. Biol. 33, 537–553, http://dx. doi.org/10.1146/annurev-cellbio-100616-060818. Martínez-Martínez, M.Á., De Juan Romero, C., Fernández, V., Cárdenas, A., Götz, M., Borrell, V., 2016. A restricted period for formation of outer subventricular zone defined by Cdh1 and Trnp1 levels. Nat. Commun. 7, 11812, http://dx.doi.org/10. 1038/ncomms11812. McConnell, S.K., 1991. The generation of neuronal diversity in the central nervous system. Annu. Rev. Neurosci. 14, 269–300, http://dx.doi.org/10.1146/annurev. ne.14.030191.001413. McConnell, S.K., Kaznowski, C.E., 1991. Cell cycle dependence of laminar determination in developing neocortex. Science (80-.) 254, 282–285. McLean, C.Y., Reno, P.L., Pollen, A.A., Bassan, A.I., Capellini, T.D., Guenther, C., Indjeian, V.B., Lim, X., Menke, D.B., Schaar, B.T., Wenger, A.M., et al., 2011. Human-specific loss of regulatory DNA and the evolution of human-specific traits. Nature 471, 216–219, http://dx.doi.org/10.1038/nature09774. Mefford, H.C., Eichler, E.E., 2009. Duplication hotspots, rare genomic disorders, and common disease. Curr. Opin. Genet. Dev. 19, 196–204, http://dx.doi.org/10. 1016/j.gde.2009.04.003. Mekel-bobrov, N., Gilbert, S.L., Evans, P.D., Vallender, E.J., Anderson, J.R., Hudson, R.R., Tishkoff, S.A., Lahn, B.T., 2005. Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens. Science (80-.) 309, 1720–1722. Mihalas, A.B., Elsen, G.E., Bedogni, F., Daza, R.A.M., Ramos-Laguna, K.A., Arnold, S.J., Hevner, R.F., 2016. Intermediate progenitor cohorts differentially generate cortical layers and require Tbr2 for timely acquisition of neuronal subtype identity. Cell Rep. 16, 92–105, http://dx.doi.org/10.1016/j.celrep.2016.05.072. Miller, Ja., Ding, S.-L., Sunkin, S.M., Smith, Ka., Ng, L., Szafer, A., Ebbert, A., Riley, Z.L., Royall, J.J., Aiona, K., Arnold, J.M., et al., 2014. Transcriptional landscape of the prenatal human brain. Nature 508, 199–206, http://dx.doi.org/10.1038/ nature13185. Miyata, T., Kawaguchi, A., Saito, K., Kawano, M., Muto, T., Ogawa, M., 2004. Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells. Development 131, 3133–3145, http://dx.doi.org/10.1242/dev.01173. Miyata, T., Kawaguchi, D., Kawaguchi, A., Gotoh, Y., 2010. Mechanisms that regulate the number of neurons during mouse neocortical development. Curr. Opin. Neurobiol. 20, 22–28, http://dx.doi.org/10.1016/j.conb.2010.01.001. Mizutani, K., Saito, T., 2005. Progenitors resume generating neurons after temporary inhibition of neurogenesis by Notch activation in the mammalian cerebral. Development, 1295–1304, http://dx.doi.org/10.1242/dev.01693. Montgomery, S., 2018. Hominin brain evolution: the only way is up? Curr. Biol. 28, R788–R790, http://dx.doi.org/10.1016/j.cub.2018.06.021. Montgomery, S.H., Mundy, N.I., Barton, R.A., 2014. ASPM and mammalian brain evolution: a case study in the difficulty in making macroevolutionary inferences about gene − phenotype associations. Proc. Biol. Sci. Montgomery, S.H., Mundy, N.I., Capellini, I., Barton, R.A., Venditti, C., 2010. Adaptive evolution of four microcephaly genes and the evolution of brain size in anthropoid Primates. Mol. Biol. Evol. 28, 625–638, http://dx.doi.org/10.1093/molbev/ msq237. Montiel, J.F., Molnár, Z., 2013. The impact of gene expression analysis on evolving views of avian brain organization. J. Comp. Neurol. 521, 3604–3613, http://dx. doi.org/10.1002/cne.23403. Mora-Bermúdez, F., Badsha, F., Kanton, S., Camp, J.G., Vernot, B., Köhler, K., Voigt, B., Okita, K., Maricic, T., He, Z., Lachmann, R., et al., 2016. Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development. Elife 5, e18683, http://dx.doi.org/10.7554/eLife.18683. Mosca, S., Raponi, M., Meneghello, A., Buratti, E., Woods, C.G., Baralle, D., 2017. Human NDE1 splicing and mammalian brain development. Sci. Rep. 7, 43504, http://dx.doi.org/10.1038/srep43504. Nobrega, M.A., Ovcharenko, I., Afzal, V., Rubin, E.M., 2003. Scanning human gene deserts for long-range enhancers. Science (80-.) 302, 413, http://dx.doi.org/10. 1126/science.1088328. ˜ V., Ivic, L., Kriegstein, A.R., 2004. Cortical neurons Noctor, S.C., Martínez-cerdeno, arise in symmetric and asymmetric division zones and migrate through specific phases. Nat. Neurosci. 7, 136–144, http://dx.doi.org/10.1038/nn1172. Nomura, T., Ohtaka-Maruyama, C., Yamashita, W., Wakamatsu, Y., Murakami, Y., Calegari, F., Suzuki, K., Gotoh, H., Ono, K., 2016. The evolution of basal progenitors in the developing non-mammalian brain. Development 143, 66–74, http://dx. doi.org/10.1242/dev.127100. Nomura, T., Takahashi, M., Hara, Y., Osumi, N., 2008. Patterns of neurogenesis and amplitude of reelin expression are essential for making a mammalian-type cortex. PLoS One 3, e1454, http://dx.doi.org/10.1371/journal.pone.0001454. Nonaka-Kinoshita, M., Reillo, I., Artegiani, B., Angeles Martínez-Martínez, M., Nelson, M., Borrell, V., Calegari, F., 2013. Regulation of cerebral cortex size and folding

by expansion of basal progenitors. EMBO J. 1, 1–12, http://dx.doi.org/10.1038/ emboj.2013.96. Northcutt, R.G., Kaas, J.H., 1995. The emergence and evolution of mammalian neocortex. Trends Neurosci. 18, 373–379, http://dx.doi.org/10.1016/01662236(95)93932-n. Nowakowski, T.J., Bhaduri, A., Pollen, A.A., Alvarado, B., Mostajo-Radji, M.A., Di Lullo, E., Haeussler, M., Sandoval-Espinosa, C., Liu, S.J., Velmeshev, D., Ounadjela, J.R., et al., 2017. Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex. Science (80-.) 358, 1318–1323, http://dx.doi. org/10.1126/science.aap8809. Nowakowski, T.J., Pollen, A.A., Sandoval-Espinosa, C., Kriegstein, A.R., 2016. Transformation of the radial glia scaffold demarcates two stages of human cerebral cortex development. Neuron 91, 1219–1227, http://dx.doi.org/10.1016/j.neuron.2016. 09.005. Oberst, P., Fievre, S., Baumann, N., Concetti, C., Jabaudon, D., 2018. Apical progenitors remain multipotent throughout cortical neurogenesis. bioRxiv, http://dx. doi.org/10.1101/478891, 10.1101/47. Ohno, S., 1999. Gene duplication and the uniqueness of vertebrate genomes circa 1970 – 1999. Semin. Cell Dev. Biol. 10, 517–522. Ohno, S., 1970. Evolution by Gene Duplication. London: George Alien & Unwin Ltd. Berlin, Heidelberg and New York: Springer-Verlag. Okamoto, M., Miyata, T., Konno, D., Ueda, H.R., Kasukawa, T., Hashimoto, M., Matsuzaki, F., Kawaguchi, A., 2016. Cell-cycle-independent transitions in temporal identity of mammalian neural progenitor cells. Nat. Commun. 7, 11349, http:// dx.doi.org/10.1038/ncomms11349. Otani, T., Marchetto, M.C., Gage, F.H., Simons, B.D., Livesey, F.J., 2016. 2D and 3D stem cell models of primate cortical development identify species-specific differences in progenitor behavior contributing to brain size. Cell Stem Cell 18, 467–480, http://dx.doi.org/10.1016/j.stem.2016.03.003. Pei, L., Peng, Y., Yang, Y., Ling, X.B., van Eyndhoven, W.G., Nguyen, K.C.Q., Rubin, M., Hoey, T., Powers, S., Li, J., 2002. PRC17, a novel oncogene encoding a Rab GTPaseactivating protein, is amplified in prostate cancer. Cancer Res. 62, 5420–5424. Pennacchio, L.A., Ahituv, N., Moses, A.M., Prabhakar, S., Nobrega, M.A., Shoukry, M., Minovitsky, S., Dubchak, I., Holt, A., Lewis, K.D., Plajzer-frick, I., et al., 2006. In vivo enhancer analysis of human conserved non-coding sequences. Nature 444, 499–502, http://dx.doi.org/10.1038/nature05295. Petanjek, Z., Judas, M., Simic, G., Rasin, M.R., Uylings, H.B.M., Rakic, P., Kostovic, I., ˇ ˇ 2011. Extraordinary neoteny of synaptic spines in G., Goran, S., Judaˇs, M., Simic, the human prefrontal cortex. Proc. Natl. Acad. Sci. U. S. A. 108, 13281–13286, http://dx.doi.org/10.1073/pnas.1105108108. Pollard, K.S., Salama, S.R., King, B., Kern, A.D., Dreszer, T., Katzman, S., Siepel, A., Pedersen, J.S., Bejerano, G., Baertsch, R., Rosenbloom, K.R., et al., 2006a. Forces shaping the fastest evolving regions in the human genome. PLoS Genet. 2, e168, http://dx.doi.org/10.1371/journal.pgen.0020168. Pollard, K.S., Salama, S.R., Lambert, N., Lambot, M.-A., Coppens, S., Pedersen, J.S., Katzman, S., King, B., Onodera, C., Siepel, A., Kern, A.D., et al., 2006b. An RNA gene expressed during cortical development evolved rapidly in humans. Nature 443, 167–172, http://dx.doi.org/10.1038/nature05113. Pollen, A.A., Bhaduri, A., Andrews, M.G., Haussler, D., Eichler, E.E., Kriegstein, A.R., Pollen, A.A., Bhaduri, A., Andrews, M.G., Nowakowski, T.J., Meyerson, O.S., et al., 2019. Establishing cerebral organoids as models of human-specific brain evolution. Cell 176, http://dx.doi.org/10.1016/j.cell.2019.01.017, 743-756.e17. Pollen, A.A., Nowakowski, T.J., Chen, J., Retallack, H., Sandoval-Espinosa, C., Nicholas, C.R., Shuga, J., Liu, S.J., Oldham, M.C., Diaz, A., Lim, D.A., et al., 2015. Molecular identity of human outer radial glia during cortical development. Cell 163, 55–67, http://dx.doi.org/10.1016/j.cell.2015.09.004. Prabhakar, S., Noonan, J.P., Pääbo, S., Rubin, E.M., 2006. Accelerated evolution of conserved noncoding sequences in humans. Science (80-.) 314, 786-, http://dx. doi.org/10.1126/science.1130738. Prabhakar, S., Visel, A., Akiyama, J.A., Shoukry, M., Lewis, K.D., Holt, A., Plajzer-frick, I., Morrison, H., Fitzpatrick, D.R., Afzal, V., et al., 2008. Human-specific gain of function in a developmental enhancer. Science (80-.) 7811, 1346–1351. Puzzolo, E., Mallamaci, A., 2010. Cortico-cerebral histogenesis in the opossum Monodelphis domestica: generation of a hexalaminar neocortex in the absence of a basal proliferative compartment. Neural Dev. 5, 8, http://dx.doi.org/10.1186/ 1749-8104-5-8. Rakic, P., 2009. Evolution of the neocortex: a perspective from developmental biology. Nat. Rev. Neurosci. 10, 724–735, http://dx.doi.org/10.1038/nrn2719. Rakic, P., 1995. A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution. Trends Neurosci. 18, 383–388, http:// dx.doi.org/10.1016/0166-2236(95)93934-P. Rash, B.G., Tomasi, S., Lim, H.D., Suh, C.Y., Vaccarino, F.M., 2013. Cortical gyrification induced by fibroblast growth factor 2 in the mouse brain. J. Neurosci. 33, 10802–10814, http://dx.doi.org/10.1523/JNEUROSCI.3621-12.2013. Reillo, I., Borrell, V., 2012. Germinal zones in the developing cerebral cortex of ferret: ontogeny, cell cycle kinetics, and diversity of progenitors. Cereb. Cortex 22, 2039–2054, http://dx.doi.org/10.1093/cercor/bhr284. Reilly, S.K., Yin, J., Ayoub, a.E., Emera, D., Leng, J., Cotney, J., Sarro, R., Rakic, P., Noonan, J.P., 2015. Evolutionary changes in promoter and enhancer activity during human corticogenesis. Science (80-.) 347, 1155–1159, http://dx.doi.org/10. 1126/science.1260943. Reimers-Kipping, S., Hevers, W., Pääbo, S., Enard, W., 2011. Humanized Foxp2 specifically affects cortico-basal ganglia circuits. Neuroscience 175, 75–84, http://dx. doi.org/10.1016/j.neuroscience.2010.11.042. Ruiz-Orera, J., Hernandez-Rodriguez, J., Chiva, C., Sabidó, E., Kondova, I., Bontrop, R., Marqués-Bonet, T., Albà, M.M., 2015. Origins of de novo genes in human and

Please cite this article in press as: I.K. Suzuki, Molecular drivers of human cerebral cortical evolution. Neurosci. Res. (2019), https://doi.org/10.1016/j.neures.2019.05.007

G Model NSR-4289; No. of Pages 14

ARTICLE IN PRESS I.K. Suzuki / Neuroscience Research xxx (2019) xxx–xxx

chimpanzee. PLoS Genet. 11, e1005721, http://dx.doi.org/10.1371/journal.pgen. 1005721. Sakai, T., Hirata, S., Fuwa, K., Sugama, K., Kusunoki, K., Makishima, H., Eguchi, T., Yamada, S., Ogihara, N., 2012. Fetal brain development in chimpanzees versus humans. Curr. Biol. 22, R791–R792, http://dx.doi.org/10.1016/j.cub.2012. 06.062. Sakai, T., Matsui, M., Mikami, A., Malkova, L., Hamada, Y., Tomonaga, M., Suzuki, J., Tanaka, M., Miyabe-nishiwaki, T., Makishima, H., Nakatsukasa, M., 2013. Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain. Proc. R. Soc. B, http://dx.doi.org/10.1098/rspb.2012.2398. Sakai, T., Mikami, A., Tomonaga, M., Matsui, M., Suzuki, J., Hamada, Y., Tanaka, M., Miyabe-Nishiwaki, T., Makishima, H., Nakatsukasa, M., Matsuzawa, T., 2011. Differential prefrontal white matter development in chimpanzees and humans. Curr. Biol. 21, 1397–1402, http://dx.doi.org/10.1016/j.cub.2011.07.019. Sauerland, C., Menzies, B.R., Glatzle, M., Seeger, J., Renfree, M.B., Fietz, S.A., 2018. The basal radial glia occurs in marsupials and underlies the evolution of an expanded neocortex in therian mammals. Cereb. Cortex 28, 145–157, http://dx.doi.org/10. 1093/cercor/bhw360. Schlotterer, C., 2015. Genes from scratch – the evolutionary fate of de novo genes. Trends Genet. 31, 215–219, http://dx.doi.org/10.1016/j.tig.2015.02.007. Schmidt, D., Wilson, M.D., Ballester, B., Schwalie, P.C., Brown, G.D., Marshall, A., Kutter, C., Watt, S., Martinez-Jimenez, C.P., Mackay, S., Talianidis, I., et al., 2010. Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Science (80-.), http://dx.doi.org/10.1126/science.1186176. Schreiweis, C., Bornschein, U., Burguière, E., Kerimoglu, C., Schreiter, S., 2014. Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance. Proc. Natl. Acad. Sci. U. S. A. 111, 14253–14258, http://dx.doi.org/10.1073/pnas.1414542111. ˇ N., Sestan, N., 2012. Cis-regulatory Shim, S., Kwan, K.Y., Li, M., Lefebvre, V., Sestan, control of corticospinal system development and evolution. Nature 486, 74–79, http://dx.doi.org/10.1038/nature11094. Shitamukai, A., Konno, D., Matsuzaki, F., 2011. Oblique radial glial divisions in the developing mouse neocortex induce self-renewing progenitors outside the germinal zone that resemble primate outer subventricular zone progenitors. J. Neurosci. 31, 3683–3695, http://dx.doi.org/10.1523/JNEUROSCI.4773-10.2011. Shubin, N., Tabin, C., Carroll, S., 2009. Deep homology and the origins of evolutionary novelty. Nature 457, 818–823, http://dx.doi.org/10.1038/nature07891. Smith, R.S., Kenny, C.J., Ganesh, V., Jang, A., Borges-Monroy, R., Partlow, J.N., Hill, R.S., Shin, T., Chen, A.Y., Doan, R.N., 2018. Sodium channel SCN3A (NaV1. 3) regulation of human cerebral cortical folding and oral motor development. Neuron 99, 905–913. Somel, M., Franz, H., Yan, Z., Lorenc, A., Guo, S., Giger, T., Kelso, J., Nickel, B., Dannemann, M., Bahn, S., Webster, M.J., et al., 2009. Transcriptional neoteny in the human brain. Proc. Natl. Acad. Sci. U. S. A. 106, 5743–5748, http://dx.doi.org/10. 1073/pnas.0900544106. Sone, J., Mitsuhashi, S., Fujita, A., Mizuguchi, T., Mori, K., Koike, H., Hashiguchi, A., Takashima, H., Sugiyama, H., Kohno, Y., Takiyama, Y., et al., 2019. Long-read sequencing identifies GGC repeat expansion in human-specific NOTCH2NLC associated with neuronal intranuclear inclusion disease. bioRxiv, http://dx.doi. org/10.1101/515635, 515635. Sousa, AndréM.M., Zhu, Y., Raghanti, M.A., Kitchen, R.R., Onorati, M., Tebbenkamp, A.T.N., Stutz, B., Meyer, K.A., Li, M., Kawasawa, Y.I., Liu, F., et al., 2017. Molecular and cellular reorganization of neural circuits in the human lineage. Science (80-.) 358, 1027–1032. Sporny, M., Guez-haddad, J., Kreusch, A., Shakartzi, S., Neznansky, A., Cross, A., Isupov, M.N., Qualmann, B., Kessels, M.M., Opatowsky, Y., Mina, T., et al., 2017. Structural history of human SRGAP2 proteins. Mol. Biol. Evol. 34, 1463–1478, http://dx.doi.org/10.1093/molbev/msx094. Stahl, R., Walcher, T., De Juan Romero, C., Pilz, G.A.A., Cappello, S., Irmler, M., SanzAquela, J.M.M., Beckers, J., Blum, R., Borrell, V., Götz, M., et al., 2013. Trnp1 regulates expansion and folding of the mammalian cerebral cortex by control of radial glial fate. Cell 153, 535–549, http://dx.doi.org/10.1016/j.cell.2013.03.027. Stankiewicz, P., Lupski, J.R., 2010. Structural variation in the human genome and its role in disease. Annu. Rev. Med. 61, 437–455, http://dx.doi.org/10.1146/ annurev-med-100708-204735. Sudmant, P.H., Huddleston, J., Catacchio, C.R., Malig, M., Hillier, L.W., Baker, C., Mohajeri, K., Kondova, I., Bontrop, R.E., Persengiev, S., Antonacci, F., et al., 2013. Evolution and diversity of copy number variation in the great ape lineage. Genome Res. 23, 1373–1382, http://dx.doi.org/10.1101/gr.158543.113. Sudmant, P.H., Kitzman, J.O., Antonacci, F., Alkan, C., Malig, M., Tsalenko, A., Sampas, N., Bruhn, L., Shendure, J., Eichler, E.E., 2010. Diversity of human copy number variation and multicopy genes. Science (80-.) 330, 641–646, http://dx.doi.org/ 10.1126/science.1197005. Suzuki, I.K., Gacquer, D., Van Heurck, R., Kumar, D., Wojno, M., Bilheu, A., Herpoel, A., Lambert, N., Cheron, J., Polleux, F., Detours, V., Vanderhaeghen, P., 2018. Humanspecific NOTCH2NL genes expand cortical neurogenesis through delta/notch regulation. Cell 173, 1370–1384, http://dx.doi.org/10.1016/j.cell.2018.03.067. Suzuki, I.K., Hirata, T., 2014. A common developmental plan for neocortical geneexpressing neurons in the pallium of the domestic chicken Gallus gallus domesticus and the Chinese softshell turtle Pelodiscus sinensis. Front. Neuroanat. 8, 1–6, http://dx.doi.org/10.3389/fnana.2014.00020. Suzuki, I.K., Hirata, T., 2013. Neocortical neurogenesis is not really “neo”: a new evolutionary model derived from a comparative study of chick pallial development. Dev. Growth Differ. 55, 173–187, http://dx.doi.org/10.1111/dgd.12020.

13

Suzuki, I.K., Hirata, T., 2012. Evolutionary conservation of neocortical neurogenetic program in the mammals and birds. Bioarchitecture 2, 124–129, http://dx.doi. org/10.4161/bioa.21032. Suzuki, I.K., Kawasaki, T., Gojobori, T., Hirata, T., 2012. The temporal sequence of the mammalian neocortical neurogenetic program drives mediolateral pattern in the chick pallium. Dev. Cell 22, 863–870, http://dx.doi.org/10.1016/j.devcel. 2012.01.004. Suzuki, I.K., Vanderhaeghen, P., 2019. Evolving brains with new genes. Opera Med. Physiol. 4, in press. Suzuki, I.K., Vanderhaeghen, P., 2015. Is this a brain which i see before me? Modeling human neural development with pluripotent stem cells. Development 142, http://dx.doi.org/10.1242/dev.120568. Tautz, D., Domazet-loˇso, T., 2011. The evolutionary origin of orphan genes. Nat. Rev. Genet. 12, 692–702, http://dx.doi.org/10.1038/nrg3053. Telley, L., Agirman, G., Prados, J., Fievre, S., Oberst, P., Vitali, I., Nguyen, L., Dayer, A., Jabaudon, D., 2018. Single-cell transcriptional dynamics and origins of neuronal diversity in the developing mouse neocortex. bioRxiv, http://dx.doi.org/ 10.1101/409458. Telley, L., Govindan, S., Prados, J., Stevant, I., Nef, S., Dermitzakis, E., Dayer, A., Jabaudon, D., 2016. Sequential transcriptional waves direct the differentiation of newborn neurons in the mouse neocortex. Science (80-.) 351, 1443–1446, http://dx.doi.org/10.1126/science.aad8361. Toll-riera, M., Bosch, N., Castelo, R., Armengol, L., Estivill, X., Alba, M.M., 2009. Origin of primate orphan genes: a comparative genomics approach. Mol. Biol. Evol. 26, 603–612, http://dx.doi.org/10.1093/molbev/msn281. Vaid, S., Camp, J.G., Hersemann, L., Eugster Oegema, C., Heninger, A.K., Winkler, S., Brandl, H., Sarov, M., Treutlein, B., Huttner, W.B., Namba, T., 2018. A novel population of Hopx-dependent basal radial glial cells in the developing mouse neocortex. Development 145, http://dx.doi.org/10.1242/dev.169276. Villar, D., Berthelot, C., Aldridge, S., Rayner, T.F., Lukk, M., Pignatelli, M., Park, T.J., Deaville, R., Erichsen, J.T., Jasinska, A.J., Turner, J.M.A., et al., 2015. Enhancer evolution across 20 mammalian species. Cell 160, 554–566, http://dx.doi.org/10. 1016/j.cell.2015.01.006. Visel, A., Blow, M.J., Li, Z., Zhang, T., Akiyama, J.A., Holt, A., Plajzer-Frick, I., Shoukry, M., Wright, C., Chen, F., Afzal, V., et al., 2009. ChIP-seq accurately predicts tissuespecific activity of enhancers. Nature 457, 854–858, http://dx.doi.org/10.1038/ nature07730. Visel, A., Minovitsky, S., Dubchak, I., Pennacchio, L.A., 2007. VISTA Enhancer Browser — a database of tissue-specific human enhancers. Nucleic Acids Res. 35, 88–92, http://dx.doi.org/10.1093/nar/gkl822. Visel, A., Prabhakar, S., Akiyama, J.A., Shoukry, M., Lewis, K.D., Holt, A., Plajzerfrick, I., Afzal, V., Rubin, E.M., 2008. Ultraconservation identifies a small subset of extremely constrained developmental enhancers. Nat. Genet. 40, 158–160, http://dx.doi.org/10.1038/ng.2007.55. Vitali, I., Fie, S., Telley, L., Bellone, C., Silver, D.L., Jabaudon, D., Telley, L., Oberst, P., Bariselli, S., Frangeul, L., 2018. Progenitor hyperpolarization regulates the sequential generation of neuronal subtypes in the developing neocortex. Cell 174, 1264–1276, http://dx.doi.org/10.1016/j.cell.2018.06.036. Wainszelbaum, M.J., Charron, A.J., Kong, C., Kirkpatrick, D.S., Srikanth, P., Barbieri, M.A., Gygi, S.P., Stahl, P.D., 2008. The hominoid-specific oncogene TBC1D3 activates Ras and modulates epidermal growth factor receptor signaling and trafficking. J. Biol. Chem. 283, 13233–13242, http://dx.doi.org/10.1074/jbc. M800234200. Wang, H.-Y., Chien, H.-C., Osada, N., Hashimoto, K., Sugano, S., Gojobori, T., Chou, C.K., Tsai, S.-F., Wu, C.-I., Shen, C.-K.J., 2006. Rate of evolution in brain-expressed genes in humans and other Primates. PLoS Biol. 5, e13. Wang, J., Lu, Z.X., Tokheim, C.J., Miller, S.E., Xing, Y., 2015. Species-specific exon loss in human transcriptomes. Mol. Biol. Evol. 32, 481–494, http://dx.doi.org/10.1093/ molbev/msu317. Wang, L., Hou, S., Han, Y.-G., 2016. Hedgehog signaling promotes basal progenitor expansion and the growth and folding of the neocortex. Nat. Neurosci. 19, 888–896, http://dx.doi.org/10.1038/nn.4307. Wang, X., Tsai, J., LaMonica, B., Kriegstein, A.R., 2011. A new subtype of progenitor cell in the mouse embryonic neocortex. Nat. Neurosci. 14, 555–561, http://dx. doi.org/10.1038/nn.2807. Weischenfeldt, J., Symmons, O., Spitz, F., Korbel, J.O., 2013. Phenotypic impact of genomic structural variation: insights from and for human disease. Nat. Rev. Genet. 14, 125–138, http://dx.doi.org/10.1038/nrg3373. Wilsch-Brauninger, M., Florio, M., Huttner, W.B., 2016. Neocortex expansion in development and evolution - from cell biology to single genes. Curr. Opin. Neurobiol. 39, 122–132, http://dx.doi.org/10.1016/j.conb.2016.05.004. Won, H., de la Torre-Ubieta, L., Stein, J.L., Parikshak, N.N., Huang, J., Opland, C.K., Gandal, M.J., Sutton, G.J., Hormozdiari, F., Lu, D., Lee, C., et al., 2016. Chromosome conformation elucidates regulatory relationships in developing human brain. Nature 538, 523–527, http://dx.doi.org/10.1038/nature19847. Workman, a.D., Charvet, C.J., Clancy, B., Darlington, R.B., Finlay, B.L., 2013. Modeling transformations of neurodevelopmental sequences across mammalian species. J. Neurosci. 33, 7368–7383, http://dx.doi.org/10.1523/JNEUROSCI.574612.2013. Wu, D., Irwin, D.M., Zhang, Y., 2011. De novo origin of human protein-coding genes. PLoS Genet. 7, e1002379, http://dx.doi.org/10.1371/journal.pgen.1002379. Wu, X., Sharp, P.A., 2013. Divergent transcription: a driving force for new gene origination? Cell 155, 990–996, http://dx.doi.org/10.1016/j.cell.2013.10.048. Xie, C., Zhang, Y.E., Chen, J., Liu, C., Zhou, W., Li, Y., Zhang, M., 2012. Hominoidspecific de novo protein-coding genes originating from long non-coding RNAs. PLoS Genet. 8, e1002942, http://dx.doi.org/10.1371/journal.pgen.1002942.

Please cite this article in press as: I.K. Suzuki, Molecular drivers of human cerebral cortical evolution. Neurosci. Res. (2019), https://doi.org/10.1016/j.neures.2019.05.007

G Model NSR-4289; No. of Pages 14 14

ARTICLE IN PRESS I.K. Suzuki / Neuroscience Research xxx (2019) xxx–xxx

Xu, S., Chen, Y., Cheng, Y., Yang, D., Zhou, X., Xu, J., Zhou, K., Yang, G., 2012. Positive selection at the ASPM gene coincides with brain size enlargements in cetaceans. Proc. Biol. Sci., http://dx.doi.org/10.1098/rspb.2012.1729. Yoon, K., Ringeling, F.R., Vissers, C., He, C., Yoon, K., Ringeling, F.R., Vissers, C., Jacob, F., Pokrass, M., Jin, P., Regot, S., et al., 2017. Temporal control of mammalian cortical neurogenesis by m 6 A methylation article temporal control of mammalian cortical neurogenesis by m 6 A methylation. Cell 171, 877–889, http://dx.doi. org/10.1016/j.cell.2017.09.003. Zhang, J., 2003. Evolution of the human ASPM gene, a major determinant of brain size. Nature 2070, 2063–2070.

Zhang, J., Webb, D.M., Podlaha, O., 2002. Accelerated protein evolution and origins of human-specific features: FOXP2 as an example. Genetics 162, 1825–1835. Zhong, S., Zhang, S., Fan, X., Wu, Q., Yan, L., Dong, J., Zhang, H., Li, L., Sun, L., 2018. A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex. Nature 555, 524–528, http://dx.doi.org/10.1038/nature25980. Zhu, Y., Sousa, A.M.M., Gao, T., Skarica, M., Li, M., Santpere, G., Esteller-cucala, P., Juan, D., Ferrández-peral, L., Gulden, F.O., Yang, M., Miller, D.J., et al., 2018. Spatiotemporal transcriptomic divergence across human and macaque brain development. Science (80-.) 362, 1267–1282, http://dx.doi.org/10.1126/science.aat8077.

Please cite this article in press as: I.K. Suzuki, Molecular drivers of human cerebral cortical evolution. Neurosci. Res. (2019), https://doi.org/10.1016/j.neures.2019.05.007