Development and evolution of cortical fields

Neuroscience Research 86 (2014) 66–76

Contents lists available at ScienceDirect

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

Review article

Development and evolution of cortical fields Yoko Arai ∗ , Alessandra Pierani Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris Cedex, France

a r t i c l e

i n f o

Article history: Received 1 February 2014 Received in revised form 5 June 2014 Accepted 10 June 2014 Available online 28 June 2014 Keywords: Neurogenesis Cortical patterning Cajal–Retzius neurons Thalamo-cortical afferents Evolution Cortical areas

a b s t r a c t The neocortex is the brain structure that has been subjected to a major size expansion, in its relative size, during mammalian evolution. It arises from the cortical primordium through coordinated growth of neural progenitor cells along both the tangential and radial axes and their patterning providing spatial coordinates. Functional neocortical areas are ultimately consolidated by environmental influences such as peripheral sensory inputs. Throughout neocortical evolution, cortical areas have become more sophisticated and numerous. This increase in number is possibly involved in the complexification of neocortical function in primates. Whereas extensive divergence of functional cortical fields is observed during evolution, the fundamental mechanisms supporting the allocation of cortical areas and their wiring are conserved, suggesting the presence of core genetic mechanisms operating in different species. We will discuss some of the basic molecular mechanisms including morphogen-dependent ones involved in the precise orchestration of neurogenesis in different cortical areas, elucidated from studies in rodents. Attention will be paid to the role of Cajal–Retzius neurons, which were recently proposed to be migrating signaling units also involved in arealization, will be addressed. We will further review recent works on molecular mechanisms of cortical patterning resulting from comparative analyses between different species during evolution. © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Contents 1. 2.

3.

4.

5.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Radial organization of the cerebral cortex: neurogenesis during evolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Changes in cortical proliferative regions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Proliferative capacities and cell-cycle kinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Proliferative capacities and environmental influences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Tangential organization of the cerebral cortex: cortical patterning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Morphogens and transcription factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Extrinsic influences: Cajal–Retzius neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Extrinsic influences: thalamo-cortical afferents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Evolution of cortical fields . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Comparative anatomy of cortical areas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Genomic and transcriptomic changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3. CR neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions and perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

67 67 67 67 68 69 69 69 69 71 71 73 73 74 74 74

Abbreviations: NE, neuroepithelial cells; RG, radial glial cells; V1, primary visual area; A1, primary auditory area; S1, primary somatosensory area; M1, primary motor area; AP, anteroposterior; DV, dorsoventral; VP, ventral pallium; PSB, pallial sub-pallial boundary; TCA, thalamo-cortical afferents; VHO , higher-order visual area; SGL, subpial granular layer cells. ∗ Corresponding author. Tel.: +33 1 57 27 81 26; fax: +33 1 57 27 80 87. E-mail address: [email protected] (Y. Arai). http://dx.doi.org/10.1016/j.neures.2014.06.005 0168-0102/© 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Y. Arai, A. Pierani / Neuroscience Research 86 (2014) 66–76

1. Introduction The mammalian neocortex, which is the control center of our cognitive functions, responsible for behavior and social activities, is the brain structure that shows major expansion during evolution. The neocortex arises from the dorsal telencephalon and is composed by different types of neurons that are generated after the exponential expansion of neural stem cells known as neuroepithelial cells (NE) and which later differentiate into radial glial cells (RG). Among the features, which are unique to the neocortex as opposed to other brain regions, is the radial neuronal organization in six major layers, composed of earlier and later born neurons positioned according to an inside-out sequence. Each layer contains multiple distinct neuronal populations and functionally distinct connectivity. The neocortex shows a spatial organization (in the tangential dimension) called arealization, which represents the subdivision of the neocortex into functionally distinct cortical areas. The basic plan of a mammalian neocortex is constituted by four primary areas: visual (V1), auditory (A1), somatosensory (S1) and motor (M1) cortices. Primary areas relay input information from the periphery (visual, auditory and somatosensory) and control motor output. These are functionally interconnected to “higher-order areas” that act as specialized processing or integrating centers (O’Leary and Sahara, 2008; Krubitzer and Dooley, 2013); the latter being largely added during neocortex evolution. Area identity starts to be established early during development but its ultimate determination depends also on environmental cues brought notably by peripheral axons branching in cortical areas (O’Leary, 1989; O’Leary et al., 1994). During evolution, different neocortical territories expanded unequally. Species-specific neocortical areas were formed and coincidentally region-specific expression of genes was also reported (Abrahams et al., 2007; Johnson et al., 2009; Kang et al., 2011; Chen et al., 2011), suggesting a convergent evolution between brain structure and gene regulation. Causal or as a consequence of anatomical changes, increasing neuronal complexity and plasticity is also pronounced during evolution. For instance, the morphology of human pyramidal neurons and their plasticity in response to environmental cues show extensive changes with area-specific differences (Elston et al., 2001; Van Pelt and Uylings, 2002; Elston, 2003). Thus, the area-specific degree of neuronal maturation is likely involved in functional specification of the human brain. To understand the involvement of genetic and environmental factors in controlling the size and unequal expansion of cortical areas of the mammalian neocortex, in this review, we will first discuss some fundamental mechanisms involved in the establishment of early cortical patterning during development and differences that may have arisen during the course of cortical evolution.

67

Cortical neurons arise from NE, multipotent neural progenitor cells characterized by their (i) self-renewing capacity and (ii) their potential to give rise to three major neural cell types: neurons, astrocytes and oligodendrocytes (Bertrand et al., 2002; Jandial et al., 2008). NE are highly polarized cells arranged in a single layer that forms the ventricular zone (VZ) (Bystron et al., 2008). The VZ is colonized by blood vessels. On one side it faces the ventricles filled with lipoprotein- and membrane particle-rich cerebrospinal fluid, and on the other the basal lamina, a rich source of extracellular molecules (Vaccarino et al., 1999; Raballo et al., 2000; Götz and Huttner, 2005). This highly dynamic and rich micro-environment provides “stem cell niche–like” features to the NE during development (Lehtinen and Walsh, 2011), crucial for the regulation of neurogenesis and neuronal diversity. Following the onset of cortical neurogenesis, a “secondary” proliferative region, the subventricular zone (SVZ), is formed from NE cells. SVZ progenitor cells continue to proliferate for approximately one-two rounds of divisions in mice before undergoing self-consuming divisions that give rise to neurons (Noctor et al., 2004; Miyata et al., 2004; Haubensak et al., 2004; Shitamukai et al., 2011; Wang et al., 2011). The SVZ is further divided into an inner (ISVZ) and outer SVZ (OSVZ) in primates and carnivoras, which corresponds to an anatomical separation by the inner fiber tract (Reillo et al., 2011; Smart et al., 2002). OSVZ progenitor cells undergo multiple rounds of self-proliferative division followed by the direct generation of neurons (Hansen et al., 2010; Fietz et al., 2010; LaMonica et al., 2013; Betizeau et al., 2013). The anatomical appearance of the OSVZ is not unique to primates but is rather common across mammalian species which have a gyrencephalic neocortex (Smart et al., 2002; Hansen et al., 2010; Fietz et al., 2010; Reillo et al., 2011; Shitamukai and Matsuzaki, 2012). During mammalian cortical evolution, the number of cortical plate neurons has massively increased, in particular the upper (supragranular) layer neurons (layers 2–3), which comprise a larger proportion of the cortex in humans compared to rodents (Hill and Walsh, 2005). Several reports have correlated this increase with the massive enhancement of specific types of progenitor cells found in the OSVZ (Smart et al., 2002; Hansen et al., 2010; Fietz et al., 2010); therefore, this acquisition and expansion of OSVZ progenitor cells is often considered as an evolutionary adaptive change. The size of the OSVZ is correlated with the increase in neocortical size. Is it a consequence of prolonged neurogenesis mediated by different environmental influences or is it caused first by intrinsic changes in cell-cycle kinetics? To answer these questions, several studies analyzed the dynamics of the cell-cycle in distinct progenitor cells in different species (Lukaszewicz et al., 2005; Arai et al., 2011; Reillo and Borrell, 2012; Betizeau et al., 2013). 2.2. Proliferative capacities and cell-cycle kinetics

2. Radial organization of the cerebral cortex: neurogenesis during evolution 2.1. Changes in cortical proliferative regions To build up cytoarchitectonically and functionally different brains as observed during evolution, various genetic and cell biological processes are involved. Changes in the number of neurons generated may rely on changes in the proliferative capacities of the progenitor zone, which can occur through changes of intrinsic cell-cycle kinetics, and/or modifying the access of progenitor cells to environmental factors. Indeed, the mammalian neocortex has complexified its proliferative domains in the course of evolution to give rise to different sets of progenitor cells, likely having increased proliferative capacities, which may have resulted in the emergence of area-specific differences in neurogenesis.

In the mouse (a lissencephalic rodentia) at embryonic day (E) 14.5, progenitor cells in the VZ have a shorter total cell-cycle length compared to SVZ progenitor cells, due to a specific lengthening of the S phase and a shortening of the G1 phase (Pilaz et al., 2009; Arai et al., 2011). VZ and SVZ progenitor cells can both be further subdivided into proliferative and neurogenic populations (Iacopetti et al., 1999). In both VZ and SVZ, neurogenic progenitor cells have a shorter total cell-cycle length compared to that of proliferative progenitor cells, mainly due to a shorter S phase (Arai et al., 2011) (Table 1), indicating that neurogenic division is linked to a total cell-cycle shortening. Therefore, proliferative SVZ progenitor cells have the longest cell-cycle (Arai et al., 2011) and the duration of the total cell-cycle in VZ and SVZ progenitor cells is progressively increased during development in rodents (Caviness et al., 1995; Takahashi et al., 1995). In the ferret (a gyrencephalic carnivora) progenitor cells in the VZ showed no obvious differences in their total

68

Y. Arai, A. Pierani / Neuroscience Research 86 (2014) 66–76

Table 1 Distinct cell-cycle kinetics between different species. Species

Area

Stage

Neurons

TC VZ

TS (O)SVZ

TC − TS

TG1

VZ

(O)SVZ

VZ

(O)SVZ

12

21

14

23

ND ND

ND ND

20 16

24 21

≈47 ≈35

≈47 ≈35

≈51 ≈37

≈50 ≈38

Mouse

S1

E14.5

Layer 4

19

27

5

3

Ferret

V1 V1

P0 P6

Layer 2/3 Layer 2/3

42 32

43 34

22 17

18 13

Macaque

V1 V1

E65 E78

Layer 5/6 Layer 2/3

63 46

≈70 ≈50

≈12 ≈9

≈20 ≈12

VZ

(O)SVZ

An overview of cell-cycle kinetics in mouse (a lissencephalic rodentia, data from Arai et al., 2011), ferret (a gyrencephalic carnivora, data from Reillo and Borrell, 2012) and macaque monkey (a gyrencephalic primate, data from Betizeau et al., 2013) with respect to the prospective cortical area and stage analyzed. Mouse data were obtained in presumptive S1 at E14.5, a peak of layer 4 neuron generation; ferret data were obtained in presumptive V1 at P0 and P6, peaks of layer 2/3 neuron generation (see McConnell 1988); macaque data were obtained in presumptive V1 at E65 and E78, peaks of layer 5/6 and layer 2/3 generation, respectively. The thickness of OSVZ in ferret P6 is approximately 2.4 times that of P0 (see Reillo and Borrell, 2012) and in macaque around E78 is at least twice that of E65 (see Smart et al., 2002). Indicated cell-cycle parameters were a representative of all progenitor cells observed in the VZ and SVZ (mouse) or OSVZ (ferret and monkey). In mouse, the total cell-cycle is lengthened during development but it is not the case in ferret and monkey. Note: Values indicate hours. TC , total length of cell-cycle; TS , length of S phase; TG1 , length of G1 phase; TC − TS , length of total cell-cycle minus length of S phase shows the minimum time to reach the plateau of EdU or BrdU (thymidine analogs) labeling index. ND, not measured; ≈an approximated duration of cell-cycle parameters from Figure 2 in Betizeau et al. (2013). E, embryonic day; P, postnatal day; S1, primary somatosensory cortex; V1, primary visual cortex.

cell-cycle length compared to that of OSVZ progenitor cells at the same postnatal stage (Reillo and Borrell, 2012). Furthermore, VZ progenitor cells showed a longer S phase compared to OSVZ progenitor cells, suggesting that VZ progenitor cells might have either a shorter G1 or G2 + M phases or both. However, the total cell-cycle length of both VZ and OSVZ progenitor cells decreased during development with further shortening of the S phase (Reillo and Borrell, 2012), which was not the case in mice (Takahashi et al., 1995) (Table 1). In addition, a recent study using the embryonic macaque monkey (a gyrencephalic primate) has reported the presence of five distinct OSVZ progenitor cell types with differing cell-cycle dynamics (Betizeau et al., 2013). Progenitor cells in the VZ had a shorter total cell-cycle length compared to OSVZ progenitor cells at the same developmental stage seemingly due to the shortening of their S phase and showed no obvious difference of their G1 length (Betizeau et al., 2013). However, the total cell-cycle length of both VZ and OSVZ progenitor cells was shortened during development with shortening of both S and G1 phases, a similar tendency to what was observed in the ferret (Reillo and Borrell, 2012) (Table 1). Cell-cycle analyses from three different species therefore raise several points to discuss. First, the tendency of having a longer total cell-cycle length of the SVZ/OSVZ compared with VZ progenitor cells is observed in rodents and primates but it is not obvious in carnivora. According to the mammalian phylogeny, an ancestor of carnivora was separated from a common ancestor of rodents and primates (Nishihara et al., 2006), suggesting that cell-cycle lengthening of SVZ/OSVZ with respect to VZ progenitor cells might depend on a mechanism acquired or specifically conserved in the lineage of rodents and primates. Second, the shortening of the total cellcycle with the progression of development, which is observed in gyrencephalic species, may reflect the expansion of the OSVZ progenitor pool and consequently may have contributed to the massive generation of neurons observed. This may explain why a similar tendency is not found in lissencephalic rodentia. Third, it seems there are some distinct contributions of cell-cycle phases in the VZ and (O)SVZ progenitor cells between rodentia, carnivora and primates. For instance, in rodentia and carnivora, S phase length (Ts) is shorter in (O)SVZ with respect to VZ progenitor cells but it is longer in primates (Table 1). It has been suggested in mice that the lengthening of the S phase in proliferating VZ and SVZ cells reflected the DNA quality check during S phase (Arai et al., 2011). Extrapolating this to primate OSVZ progenitor cells, it suggests that they require a more robust DNA fidelity check system than that of carnivora and rodentia SVZ progenitor cells due to their extended proliferative periods. However, caution should be taken in these interspecies dataset comparisons which might indicate differences in part due

to the analysis of different cortical regions or stages rather than existing ones among species. Indeed, area specific changes in cellcycle kinetics are reported in primates. For instance, total cell-cycle length of progenitor cells in the thick OSVZ of area 17 is shorter rather than that of the thin OSVZ of area 18 in primates (macaque) (Lukaszewicz et al., 2005). The difference in the thickness of the OSVZ along the rostral–caudal axis is also reported in both ferrets and macaques (Smart et al., 2002; Reillo and Borrell, 2012); therefore, cell-cycle parameters could be variable in different cortical areas along the rostral–caudal axis. Moreover, cell-cycle analyses in the mouse were performed in the presumptive S1 at E14.5 (the peak of layer 4 generation) (Arai et al., 2011; Kwan et al., 2012) and both ferret and macaque analyses were done in presumptive area 17 (V1) in the occipital cortex coinciding with the appearance of upper layer neurons (McConnell, 1988; Reillo and Borrell, 2012; Betizeau et al., 2013). Therefore, the difference of cell-cycle kinetics that have been reported in the above three species may reflect the difference in cortical areas analyzed. Taken together, cell-cycle regulation differs in distinct subtypes of cortical progenitor cells and it is likely to be involved in regulating the number of neurons produced. Nevertheless, since cell-cycle parameters vary between different cortical regions and developmental stages, this should be considered when comparative analyses between species are performed. 2.3. Proliferative capacities and environmental influences The cell-cycle and morphological differences observed across distinct species may also be correlated with environmental changes. The morphological characteristics of OSVZ progenitor cells allow them to be exposed to more signaling molecules than the majority of mouse SVZ progenitor cells as OSVZ cells maintain a long process that spans the length of the cortical wall from the ventricle to the pia matter. For instance, Notch (Hansen et al., 2010) and Integrin signaling (Fietz et al., 2010) from the basal extracellular matrix, and Shh, FGF2 and Igf2 from the apical cerebrospinal fluid (Huang et al., 2010; Lehtinen and Walsh, 2011) have been shown to influence their proliferation. This rich environment is further complexified with the arrival of embryonic thalamo-cortical axons that have a mitotic effect on progenitor cells through the function of basic FGF (Dehay et al., 2001). These afferent fibers arrive around E14.5 in the intermediate zone in mice and are in close proximity to the SVZ, when the production of SVZ progenitor cells is still high. Then the distance between afferent fibers and proliferative VZ and SVZ zones further increases during development (Dehay et al., 2001; Dehay and Kennedy, 2007). In monkeys, thalamic axons are

Y. Arai, A. Pierani / Neuroscience Research 86 (2014) 66–76

located in the outer fiber layer above the OSVZ (Dehay and Kennedy, 2007) and the appearance of the thalamic fibers occurs much earlier in development compared to that in the mouse (Smart et al., 2002; Dehay and Kennedy, 2007). With the progression of development, fibers remain close to the OSVZ in area 17 (Smart et al., 2002; Betizeau et al., 2013). It is therefore tempting to link the two events and thus that thalamic axons might influence cell-cycle progression of OSVZ progenitor cells. However, much remains to be elucidated about the molecular aspects of the environmental proliferative cues which may act on different types of progenitor cells, and which cell-cycle parameters these influence, as well as how these may vary between different species and may have contributed to cortical evolution. 3. Tangential organization of the cerebral cortex: cortical patterning Among the key changes observed during evolution is the different size of specific cortical territories dedicated to distinct neocortical functions. The prefrontal neocortical territories, dedicated to integrative function, are preferentially expanded in the primate lineage including humans, together with associative areas, which are devoted to higher-order cortical processing (Krubitzer, 2007). However, the precise molecular mechanisms responsible for the increase of associative areas have not yet been fully investigated. 3.1. Morphogens and transcription factors The specification of cortical territories begins at early stages of development, starting from organizing centers which express different morphogens, such as Fgfs, Wnts, Bmps and Shh, and are crucial for the establishment of future cortical territories (Fig. 1a and b) (Shimamura et al., 1995; Grove et al., 1998; Assimacopoulos et al., 2003; Shimogori et al., 2004; O’Leary et al., 2007). Ectopic Fgf8 expression in the caudal cortex at an early stage of development has been shown to cause a functional duplication of cortical areas at postnatal stages (Assimacopoulos et al., 2012). Thus, the correct establishment of morphogen gradients is required for setting up cortical area identity. Cortical progenitor cells are exposed to different concentrations of morphogens (Viti et al., 2003; Lillien and Gulacsi, 2006; Toyoda et al., 2010) that function to set up the graded expression of transcription factors, such as Pax6, Emx2, COUP-TF1 and SP8 (Bishop et al., 2000; Mallamaci et al., 2000; Zembrzycki et al., 2007; Armentano et al., 2007; O’Leary et al., 2007). As a consequence, the regionalization of the dorsal telencephalon is therefore established along the anteroposterior (AP) and dorsoventral (DV) axes by E12.5 (Fig. 1c). In rodents, extensive work has been carried out to demonstrate the importance of these transcription factors in precisely controlling the positioning and size of primary cortical areas (O’Leary and Sahara, 2008). For instance, loss of function of the Emx2 and COUP-TF1 genes resulted in the reduction of caudal cortical areas (Bishop et al., 2000; Mallamaci et al., 2000; Armentano et al., 2007) and the expansion of the anterior motor cortex, whereas gain of function of Emx2 resulted in the expansion of caudal cortical areas (Hamasaki et al., 2004) (Fig. 1d). On the contrary, loss of Pax6 and Sp8 led to the expansion of the caudal V1 area and in the reduction of anterior most territories (Bishop et al., 2000, 2002; Zembrzycki et al., 2007; O’Leary et al., 2007) (Fig. 1d). The specification of neocortical areas is therefore controlled by intrinsic information in the progenitor domain in agreement with the protomap hypothesis, which postulates that progenitor cells are programmed to generate area-specific cohorts of cortical plate neurons (Rakic, 1988, 2009). Nevertheless, this expression is controlled

69

by morphogens secreted at organizing centers which are “extrinsic” to neocortical progenitors. 3.2. Extrinsic influences: Cajal–Retzius neurons In addition to the classical role of patterning centers, recent studies point to the importance of the postmitotic compartment in influencing cortical patterning (Pierani and Wassef, 2009; Borello and Pierani, 2010). Among the first-born neurons are Cajal–Retzius (CR) neurons, which are mainly generated from different organizing centers at the borders of the developing pallium: the pallial septum, the ventral pallium (VP)/pallial sub-pallial boundary (PSB) and the cortical hem (see Fig. 1b) (Takiguchi-Hayashi et al., 2004; Bielle et al., 2005; Yoshida et al., 2006; Tissir et al., 2009). Analyses of Fgf8 and Tgf␤ signaling showed the importance of organizing centers in inducing the generation of septum and cortical hem CR neurons, respectively (Siegenthaler and Miller, 2008; Zimmer et al., 2010). Depending on their origin, CR neurons express distinct molecular markers and preferentially populate specific regions of the developing cerebral cortex (Bielle et al., 2005; Yoshida et al., 2006). CR neurons, together with other pioneer neurons, form the preplate, a neuronal dense layer, which is split into two layers: the superficial marginal zone (layer 1) and the deep subplate by incoming radially migrating cortical plate neurons which will form layers 2–6 (Kwan et al., 2012). The CR neurons secrete reelin, an extracellular matrix glycoprotein and the mutation of reelin resulted in a disorganization of cortical laminar formation (D’Arcangelo et al., 1995; Ogawa et al., 1995). During early stages of development, CR neurons migrate tangentially underneath the pial surface to cover the entire cortical surface where they are also in close proximity with cortical progenitor cells. Specific ablation of a subpopulation of CR neurons derived from Dbx1-expressing cells at the pallial septum (Dbx1-derived septum CR neurons in short) results in the redistribution of CR subtypes in the rostromedial pallium between E10.5 and E11.5 and leads to arealization defects in the postnatal brain (Fig. 2a). Redistribution of CR subtypes leads to changes in the expression of Pax6 and Sp8 transcription factors within the cortical progenitor cells and in the proliferation properties of medial and dorsal cortical progenitor cells at E11.5. This early regionalization defects correlate with shifts in the positioning of cortical areas at postnatal stages. Notably, transcriptomic analysis of Dbx1-derived neurons showed that they express distinct morphogens (Griveau et al., 2010), suggesting that morphogen secretion by migrating CR cells could influence areal patterning. Thus, by signaling to cortical progenitors in the mitotic compartment, these neurons serve as organizers during development, therefore acting as “mobile signaling units”. This work points toward a novel general strategy for long-range patterning in large structures, in addition to passive diffusion of morphogens, via migration of signaling cells, a mechanism which could be of use in the expansion of the cortical surface in primates. 3.3. Extrinsic influences: thalamo-cortical afferents The relative size of cortical fields and their functional connectivity are also influenced by the environment. Cortical neurons receive information from the periphery through the thalamus via thalamocortical projections. Developmental studies of the thalamo-cortical afferents (TCA) have shown that they have a negligible effect on the size, position and molecular identity of cortical areas during mouse embryonic stages (Nakagawa et al., 1999; Garel et al., 2002). Recent studies using conditional transgenic mice have since confirmed that while no early regionalization defects occurred upon modulation of specific TCA projections, area changes in the postnatal brain were observed (Vue et al., 2013; Chou et al., 2013). In these studies, loss and gain of specific TCA projections showed that within

70

Y. Arai, A. Pierani / Neuroscience Research 86 (2014) 66–76

Fig. 1. Patterning centers in the developing mouse telencephalon, sources of CR neurons and transcription factors mediating cortical arealization. (a) Schematic representation of the developing mouse telencephalon from E10.0 to E12.5. Morphogens are secreted from signaling centers. Fgfs (Fgf8, 15 and 17) are secreted from the pallial septum (green), Wnts (Wnt2b, 3a and 5a) and Bmps (Bmp4 and 7) are secreted from the cortical hem (blue), Tgf␣, Sfrp2 and Fgf7 are expressed at the pallial-subpallial boundary (PSB or anti-hem in red). (b) Coronal views of the developing mouse forebrain showing the position of signaling centers that are highlighted in colors. These territories also represent the sites of CR subtype generation. (c) Graded expression of transcription factors (TFs) along the anterior-posterior and medial-lateral axes. While Emx2 and COUPTF1 showed rostral low/caudal high expression patterns, Pax6 and Sp8 show rostral high/caudal low expression. (d) Role of TFs in arealization by gain- and loss-of-function studies. Primary motor cortex (M1) is in green, primary somatosensory cortex (S1) in red, primary auditory cortex (A1) in orange and primary visual cortex (V1) in blue. Overexpression (OE) of Emx2 (NestinEmx2 ) leads to the expansion of V1 and an anterior shift of caudal areas. An opposite defect is observed in Emx2 knock out (KO) mice. Conditional KO of COUP-TF1 shows a massive expansion of motor cortex (M1). Small eye mutant mice (Pax6 null mice) and conditional KO of SP8 shows a reduction of rostral M1 and an anterior shift of caudal areas.

Y. Arai, A. Pierani / Neuroscience Research 86 (2014) 66–76

71

Fig. 2. Postnatal arealization defects caused by extrinsic signals. (a) Arealization defects by conditional ablation of Dbx1-derived septum Cajal–Retzius (CR) neurons. Both M1 and S1 shift laterally (dorsal view). (b) Arealization defects by conditional loss- or gain-of-function of thalamo-cortical axonal (TCA) projections derived from the dorsal lateral geniculate (dLG) nucleus in the thalamus. Loss of TCA projections causes lack of differentiation of V1. Conversely, V1 is expanded in the case of gain-of-function.

the visual field the differentiation between V1 and a surrounding higher-order visual area (VHO ) depends on TCA at postnatal day (P) 7 (Chou et al., 2013) (Fig. 2b). All together these studies show that TCA inputs are involved in refining cortical areas identity at postnatal stages (see also Pouchelon et al., 2014). However, since arrival of TCA in the developing cortex occurs at mid-gestation in mice, it leaves open the possibility that they may also function during embryogenesis and, thus, will have a double role. Several open questions still remain, such as which type of cells are first targeted by TCA to cause arealization defect later at postnatal brain either the proliferation of progenitor cells or specification of post-mitotic neurons or both, and which molecules are involved in changes in cortical patterning imprinted by TCA projections and the environment (Rakic et al., 1991; O’Leary et al., 1994; Dehay et al., 1996; Kahn and Krubitzer, 2002; Karlen et al., 2006), and if it is emphasized during evolution. In nature also there are examples which suggest that cortical arealization depends on the environmental niche and, thus, it is influenced by the use of sensory systems (Campi and Krubitzer, 2010). A comparative analysis between adult wild-caught Norway rat and Norway rat bred in the laboratory reported variations of the size of cortical fields (Campi and Krubitzer, 2010) exemplifying the impact of environmental sensory input on cortical plasticity. Despite both being the same species, wild-caught Norway rat was clearly exposed to a richer living environment than that of the laboratory. The relative size of S1 and A1 in laboratory rats was significantly bigger than that of wild-caught. In addition, although no obvious differences in V1 size were observed, a greater density of neurons was observed in wild-caught rats than in laboratory rats

(Campi et al., 2011) in this area. These results strongly suggested that the use of visual sensory system inputs change not only the size of cortical fields but also the cellular composition of the V1 cortex. It would be very interesting to know which genetic mechanisms are responsible for such changes in cortical fields and whether these alterations are partially reversible or epigenetically fixed to propagate it into the progenies, which is an important aspect from the evolutionary point of view. Altogether, many findings revealed that cortical arealization is a multi-step process initiated from early stages of development at the progenitor level, through morphogen release from signaling center and migrating CR regulating the expression of cell intrinsic transcription factors, and fine-tuned at postnatal stages by TCA projections. Peripheral stimuli and niches are involved in the proper formation of the neuronal circuitry and cortical fields which aspects might be emphasized during evolution. This might provide important cues to elucidate the interplay between niches and brain evolution.

4. Evolution of cortical fields 4.1. Comparative anatomy of cortical areas The human neocortex is different compared to that of other mammalian neocortices not only its relative size but also its structure and organization. The most pronounced total neocortical expansion is observed in anthropoid primates including humans whereas an unequal expansion of cortical areas is already detected

72

Y. Arai, A. Pierani / Neuroscience Research 86 (2014) 66–76

Fig. 3. A schematic representation of cortical area evolution. The neocortex from different mammalian species, like mouse and human, maintains basic organization of primary M1 (green), S1 (red), A1 (orange) and V1 (blue) areas (see more details in Krubitzer and Seelke, 2012), however, their allocation and relative size are variable. In humans, the size and number of anatomically distinct but functionally associated higher-order cortices are increased (indicated in white). Areas under strong genetic influences are marked by purple dots in human neocortex (see details in Chen et al., 2011). Changes in neocortical organization are initiated at the cellular level during development and, end up in sophisticated adult behavior. There are multiple steps possibly involved in the acquisition of functionally distinct areas in humans. Corresponding Brodmann’s areas are indicated in brackets.

in hominids. To better understand these changes, a categorical analysis of anatomical neocortical structures that are conserved or which diverged in mammalians, primates and hominids is necessary, as well as an understanding of their potentially divergent activities. Comparative anatomical studies reported a degree of similarity in the organization of primary cortical areas in all mammalian species examined (Krubitzer and Dooley, 2013). Furthermore, in the human fetal cerebral cortex, the expression of transcription factors involved in cortical patterning showed similar gradients compared to that in mice, strongly suggesting that fundamental anatomical features together with the basic molecular cues involved in cortical patterning are conserved across mammalian species (Bayatti et al., 2008). The main differences among mammals appear to reside in the relative size and location of the primary cortical areas and in the number of association areas (Krubitzer and Seelke, 2012) (Fig. 3). Moreover, the relative size of some cortical areas was found to be variable within the same species, and

even within the same individual, across its lifetime (Larsen and Krubitzer, 2008). Thus, the origin of this anatomical variability is multiple and relies on both the genetic background and the environment (Larsen and Krubitzer, 2008). In support of this notion, a recent study using magnetic resonance imaging (MRI) of human twins provided an estimation of the importance of genetic versus environmental influences on cortical patterning (Chen et al., 2011). The strongest genetic influence was observed around the frontal (anterior end of the frontal lobe) and temporal poles (anterior end of the temporal lobe), S1 and V1, suggesting that the remaining areas developed under environmental influences (Fig. 3). Particularly, it was emphasized that language-related Broca’s and perisylvian areas showed the highest divergence between twins (Chen et al., 2011). Therefore, intraspecies studies strongly suggest that some cortical areas are indeed influenced by the environment. This areal plasticity might also reflect the evolutionary-acquired plasticity of these specific territories and it is interesting to speculate whether

Y. Arai, A. Pierani / Neuroscience Research 86 (2014) 66–76

the human specific ability for language, considered to be the prominent neocortical function which evolved very recently, may also be the most susceptible to this plasticity. 4.2. Genomic and transcriptomic changes A high quality genomic sequence of a ca. 50,000-year-old Neanderthal woman was completed recently and showed changes of protein-coding DNA sequences compared to great apes, Denisovans and the present-day human, that may be related to language and higher cognitive functions in hominids during evolution (Prüfer et al., 2014). This study permitted to estimate the time when modern humans split from both Neanderthals and Denisovans (approximately 600,000 years ago) and Neanderthals from Denisovans (approximately 400,000 years ago) (Prüfer et al., 2014). Comparison of modern humans to Neanderthals, Denisovans and great apes, revealed 87 genes which showed non-synonymous mutations (protein coding changes), of which 90% were expressed in the developing cortex. Among these, 40% showed restricted spatiotemporal pattern of expression. Some of these genes were expressed in the developing cortex at mid-fetal stages, with a frontotemporal gradient suggesting that they might be involved in patterning of cortical areas dedicated to language and cognitive functions. Some other genes were highly enriched in the VZ suggesting stem cell maintenance functions (Prüfer et al., 2014). Similarly, specific frontotemporal expansion related to the orbitofrontal cortex (devoted to decision-making) was suggested in modern humans compared with Neanderthals using morphological analysis of skull endocasts from fossils (Pearce et al., 2013). Thus, the comparative neuroanatomy using paleontological evidence such as endocasts and hominid fossils together with molecular genetics will shed light on the “when” and “how” unique human features may have emerged and might bring about some of the molecular clues to human evolution. The genetic modifications which occurred during cortical evolution emphasized not only the change of genomic but also of transcriptomic information. Recently, the easy access to genomewide analysis techniques has allowed the revealing of differences in gene expression in areas that specifically expanded or were added in the human lineage. Lists of specific candidate genes likely to be involved in the acquisition of novel areas, for instance regions related to language acquisition (Abrahams et al., 2007) or cognitive function (Johnson et al., 2009; Kang et al., 2011), are now available. A comprehensive analysis of these datasets will bring many interesting clues to cortical area evolution. In addition to gene expression level changes, alternative isoforms can now be studied from exon-array platforms (Johnson et al., 2009) increasing the pool of possible splicing and/or transcriptional regulations involved in cortical area evolution (Johnson et al., 2009; Kang et al., 2011). For instance, an axon guidance molecule expressed both in the temporal lobe and the prefrontal cortex presented with a different enrichment of its isoforms in these two territories (Johnson et al., 2009), eventually highlighting its possible role in region-specific axonal trajectories. More insightful to human evolution, genes expressed in the neocortex in a region-specific manner were twice as likely to be associated with cis-regulatory elements that appeared to have undergone human-specific accelerated substitutions (Prabhakar et al., 2006). Such species-specific activity of cis-regulatory elements seems to be one of the molecular mechanisms for spatiotemporally controlling gene expression during evolution. 4.3. CR neurons Neocortical evolution also relies on an increase in neuronal types. As mentioned previously, a neuronal population of interest

73

are CR neurons whose number and intensity of Reelin expression has increased during cortical evolution (Meyer and Goffinet, 1998; Aboitiz et al., 2005). Marginal zone/layer 1, which CR neurons populate, is expanded in size and diversity in primates including humans (Zecevic and Rakic, 2001; Meyer, 2010), suggesting the number of CR neurons have increased in humans. The contribution of CR neurons to human evolution was emphasized by the characterization of a novel RNA gene (HAR1F), rapidly evolving in humans, that happens to be expressed by CR neurons at early stages in the future neocortex (Pollard et al., 2006). CR neurons express the secreted protein Reelin, and two types of Reelin producing cells have been characterized in humans. First layer1 is populated by Reelin-positive large neurons, and later by smaller ones in the subpial granular layer cells (SGL) (Meyer and Goffinet, 1998). It has been proposed that SGL are transiently present underneath the pial surface in the human fetal telencephalon, and are almost absent or scarce in other mammals (Meyer and Goffinet, 1998; Meyer et al., 1998), thus suggesting a complexification of layer 1 formation in primates. In addition to these morphologically distinct neurons in layer 1, a comparative study of distinct LIM transcription factor expression at the cortical hem in different species (Abellán et al., 2010) suggested a potential increase of subtypes of CR neurons in the primate layer 1 (Abellan et al., 2010) and a contribution of LIM transcription factors family in this process. Note that layer 1 include not only CR neurons but also types of neurons including GABergic interneurons (Zecevic and Rakic, 2001). Therefore, more comparative gene expression analyses will be informative to distinguish different types of neurons in layer 1 including CR neurons, and it still remains to know how many molecularly distinct CR subtypes exist in primates and whether they populate different cortical areas. In all species examined so far (turtles, crocodiles, lizard, rodent and primates including humans, see a review by Molnár et al., 2006), CR neurons express Reelin, and can also be divided into subpopulations by the expression of p73, a family member of the tumor suppressor p53 (Yang and McKeon, 2000), which marks septum and cortical hem-derived CR neurons (Meyer et al., 2002). Reelin-positive and p73-negative CR-like neurons are prominent in the lizard cortex, while the population of double positive Reelin and p73 is increased in mammals (Cabrera-Socorro et al., 2007). In parallel with the p73-positive subpopulation increase, an expansion of the cortical hem progenitor domain size was apparent in humans (Meyer and Goffinet, 1998). These observations led to the hypothesis that increased cortical hem-derived CR neurons are required to cover the enlarged surface of the human neocortex (Meyer, 2010). Furthermore, a comparison of mouse and chick telencephalon showed the presence of a novel site of Dbx1expression at the mouse VP/PSB progenitor domain, from which CR neurons originate (Bielle et al., 2005). This absence of Dbx1 expression at the VP/PSB can also be correlated to the presence of fewer CR neurons in chick than in the mouse (Bar et al., 2000; Nomura et al., 2008). Together with the capacity of the Dbx1 gene to induce the production of reelin positive cells when overexpressed ectopically (Nomura et al., 2008), it supports the idea that novel specialized progenitor domains for CR genesis may have been acquired during evolution. Another mechanism that may regulate the number of CR neurons is to switch the competence of progenitor cells devoted to the production of cortical plate neurons into CR neuron producing progenitor cells. The analysis of Fgf8 gain-of-function indicates that the ectopic Fgf8 signaling promoted the generation of CR neurons from cortical progenitor cells (Zimmer et al., 2010) and studies using Foxg1 mutant mice showed a massive increase of CR neurons, indicating that Foxg1 is a key gene controlling reversible progenitor cell competence (Muzio and Mallamaci, 2005; Hanashima et al., 2007; Kumamoto et al., 2013). In a similar line, the lack of Lhx2 expression

74

Y. Arai, A. Pierani / Neuroscience Research 86 (2014) 66–76

led also to an increase in CR neuron numbers by expanding CR generation sites (Bulchand et al., 2001; Roy et al., 2014). Although suggested by all these studies, the relevance of the increased generation of CR neurons to neocortical evolution is still to be addressed. The study of the molecular control of CR generation throughout evolution should shed light on whether and how a qualitative and/or quantitative expansion of CR neurons plays a role in the evolution of cortical areas. 5. Conclusions and perspectives The work of many laboratories points to the importance of regulating cortical patterning during neocortical development as the foundation to neocortical evolution. Cortical patterning is tightly associated with the temporal and spatial regulation of neurogenesis, which support neuronal diversity. Increasing genomic and transcriptome analyses provide comprehensive lists of genes that reveal their susceptibility to evolutionary changes. Whether these genes evolved first or as a consequence of environmental influences affecting their expressions and in turns were fixed through epigenetic mechanisms, are questions that still remain unanswered. Multi-disciplinary approaches combined with genetic manipulations, including classical mutant analysis, behavioral analysis, electrophysiological data, mathematical modeling, bioinformatics and inference from paleogenetics will be powerful to answer these evolutionary questions. In the cortical arealization field, there are still many questions which remain to be answered from the developmental and specifically evolutionary point of views. The development of imaging techniques of the neocortex allows us to better define cortical fields and functions of specific areas, and thus to more precisely understand brain network activities. Together with the increasing precision in genomic and transcriptomic information, important genes can be pinned down and evolutionary questions can be addressed. Whether cortical areas develop and evolve individually or in an orchestrated manner, it is still an open question. Whether or not these mechanisms are reversible, and whether there is some window of plasticity sustaining area formation are examples of many questions which remain to be fully investigated at the molecular level. The anatomical changes of cortical fields are linked to their neuronal connectivity. This last degree of complexity also raises relevant questions concerning species-specific behaviors and intraspecies-specific differences, particularly in humans, in the context of the susceptibility to mental diseases, which are often associated with evolutionary highlighted genes. Acknowledgements The authors apologize for not being able to cite the work of many contributors to the field. We thank Drs Eva-Maria Geigl, Melissa Barber and Veronique Dubreuil for critical reading of the manuscript. Drs Miguel Turrero Garcia, YoonJeung Chang and Jeremy Pulvers, and Misses Betty Freret-Hodara and Iffat Sumia for valuable discussions. Y.A was the recipient of fellowships from the Association pour la Recherche sur le Cancer (ARC), Fondation pour la Recherche Medicale (FRM) and Japan Society for the Promotion of Science Invitation. A.P. is a CNRS (Centre National de la Recherche Scientifique) Investigator and was supported by grants from the Agence Nationale de la Recherche (ANR-07-NEURO-046-01), FRM (DEQ20130326521) and ARC (SFI20111203674). References Abellan, A., Menuet, A., Dehay, C., Medina, L., Rétaux, S., 2010. Differential expression of LIM-homeodomain factors in Cajal-Retzius cells of primates, rodents, and birds. Cereb. Cortex (New York, N.Y.: 1991) 20, 1788–1798.

Abellán, A., Vernier, B., Rétaux, S., Medina, L., 2010. Similarities and differences in the forebrain expression of Lhx1 and Lhx5 between chicken and mouse: Insights for understanding telencephalic development and evolution. J. Comp. Neurol. 518, 3512–3528. Aboitiz, F., Montiel, J., García, R.R., 2005. Ancestry of the mammalian preplate and its derivatives: evolutionary relicts or embryonic adaptations? Rev. Neurosci. 16, 359–376. Abrahams, B.S., Tentler, D., Perederiy, J.V., Oldham, M.C., Coppola, G., Geschwind, D.H., 2007. Genome-wide analyses of human perisylvian cerebral cortical patterning. Proc. Natl. Acad. Sci. U.S.A. 104, 17849–17854. Arai, Y., Pulvers, J.N., Haffner, C., Schilling, B., Nüsslein, I., Calegari, F., Huttner, W.B., 2011. Neural stem and progenitor cells shorten S-phase on commitment to neuron production. Nat. Commun. 2, 154. Armentano, M., Chou, S.-J., Tomassy, G.S., Leingärtner, A., O’Leary, D.D.M., Studer, M., 2007. COUP-TFI regulates the balance of cortical patterning between frontal/motor and sensory areas. Nat. Neurosci. 10, 1277–1286. Assimacopoulos, S., Grove, E.A., Ragsdale, C.W., 2003. Identification of a Pax6dependent epidermal growth factor family signaling source at the lateral edge of the embryonic cerebral cortex. J. Neurosci. 23, 6399–6403. Assimacopoulos, S., Kao, T., Issa, N.P., Grove, E.A., 2012. Fibroblast growth factor 8 organizes the neocortical area map and regulates sensory map topography. J. Neurosci. Off. 32, 7191–7201. Bar, I., Lambert de Rouvroit, C., Goffinet, A.M., 2000. The evolution of cortical development. An hypothesis based on the role of the Reelin signaling pathway. Trends Neurosci. 23, 633–638. Bayatti, N., Sarma, S., Shaw, C., Eyre, J.A., Vouyiouklis, D.A., Lindsay, S., Clowry, G.J., 2008. Progressive loss of PAX6, TBR2, NEUROD and TBR1 mRNA gradients correlates with translocation of EMX2 to the cortical plate during human cortical development. Eur. J. Neurosci. 28, 1449–1456. Bertrand, N., Castro, D.S., Guillemot, F., 2002. Proneural genes and the specification of neural cell types. Nat. Rev. Neurosci. 3, 517–530. 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. Bielle, F., Griveau, A., Narboux-Nême, N., Vigneau, S., Sigrist, M., Arber, S., Wassef, M., Pierani, A., 2005. Multiple origins of Cajal-Retzius cells at the borders of the developing pallium. Nat. Neurosci. 8, 1002–1012. Bishop, K.M., Goudreau, G., O’Leary, D.D., 2000. Regulation of area identity in the mammalian neocortex by Emx2 and Pax6. Science 288, 344–349. Bishop, K.M., Rubenstein, J.L.R., O’Leary, D.D.M., 2002. Distinct actions of Emx1 Emx2, and Pax6 in regulating the specification of areas in the developing neocortex. J. Neurosci. 22, 7627–7638. Borello, U., Pierani, A., 2010. Patterning the cerebral cortex: traveling with morphogens. Curr. Opin. Genet. Dev. 20, 408–415. Bulchand, S., Grove, E.A., Porter, F.D., Tole, S., 2001. LIM-homeodomain gene Lhx2 regulates the formation of the cortical hem. Mech. Dev. 100, 165–175. Bystron, I., Blakemore, C., Rakic, P., 2008. Development of the human cerebral cortex: Boulder Committee revisited. Nat. Rev. Neurosci. 9, 110–122. Cabrera-Socorro, A., Hernandez-Acosta, N.C., Gonzalez-Gomez, M., Meyer, G., 2007. Comparative aspects of p73 and Reelin expression in Cajal-Retzius cells and the cortical hem in lizard, mouse and human. Brain Res. 1132, 59–70. Campi, K.L., Collins, C.E., Todd, W.D., Kaas, J., Krubitzer, L., 2011. Comparison of area 17 cellular composition in laboratory and wild-caught rats including diurnal and nocturnal species. Brain Behav. Evol. 77, 116–130. Campi, K.L., Krubitzer, L., 2010. Comparative studies of diurnal and nocturnal rodents: differences in lifestyle result in alterations in cortical field size and number. J. Comp. Neurol. 518, 4491–4512. Caviness Jr., V.S., Takahashi, T., Nowakowski, R.S., 1995. Numbers, time and neocortical neuronogenesis: a general developmental and evolutionary model. Trends Neurosci. 18, 379–383. Chen, C.-H., Panizzon, M.S., Eyler, L.T., Jernigan, T.L., Thompson, W., FennemaNotestine, C., Jak, A.J., Neale, M.C., Franz, C.E., Hamza, S., Lyons, M.J., Grant, M.D., Fischl, B., Seidman, L.J., Tsuang, M.T., Kremen, W.S., Dale, A.M., 2011. Genetic influences on cortical regionalization in the human brain. Neuron 72, 537–544. Chou, S.-J., Babot, Z., Leingärtner, A., Studer, M., Nakagawa, Y., O’Leary, D.D.M., 2013. Geniculocortical input drives genetic distinctions between primary and higherorder visual areas. Science 340, 1239–1242. D’Arcangelo, G., Miao, G.G., Chen, S.C., Soares, H.D., Morgan, J.I., Curran, T., 1995. A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature 374, 719–723. Dehay, C., Giroud, P., Berland, M., Killackey, H., Kennedy, H., 1996. Contribution of thalamic input to the specification of cytoarchitectonic cortical fields in the primate: effects of bilateral enucleation in the fetal monkey on the boundaries, dimensions, and gyrification of striate and extrastriate cortex. J. Comp. Neurol. 367, 70–89. Dehay, C., Kennedy, H., 2007. Cell-cycle control and cortical development. Nat. Rev. Neurosci. 8, 438–450. Dehay, C., Savatier, P., Cortay, V., Kennedy, H., 2001. Cell-cycle kinetics of neocortical precursors are influenced by embryonic thalamic axons. J. Neurosci. 21, 201–214. Elston, G.N., 2003. Cortex, cognition and the cell: new insights into the pyramidal neuron and prefrontal function. Cereb. Cortex (New York, N.Y.: 1991) 13, 1124–1138. Elston, G.N., Benavides-Piccione, R., DeFelipe, J., 2001. The pyramidal cell in cognition: a comparative study in human and monkey. J. Neurosci. 21, RC163.

Y. Arai, A. Pierani / Neuroscience Research 86 (2014) 66–76 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. Garel, S., Yun, K., Grosschedl, R., Rubenstein, J.L.R., 2002. The early topography of thalamocortical projections is shifted in Ebf1 and Dlx1/2 mutant mice. Dev. Camb. Engl. 129, 5621–5634. Götz, M., Huttner, W.B., 2005. The cell biology of neurogenesis. Nat. Rev. Mol. Cell Biol. 6, 777–788. Griveau, A., Borello, U., Causeret, F., Tissir, F., Boggetto, N., Karaz, S., Pierani, A., 2010. A novel role for Dbx1-derived Cajal-Retzius cells in early regionalization of the cerebral cortical neuroepithelium. PLoS Biol. 8, e1000440. Grove, E.A., Tole, S., Limon, J., Yip, L., Ragsdale, C.W., 1998. The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice. Dev. Camb. Engl. 125, 2315–2325. Hamasaki, T., Leingärtner, A., Ringstedt, T., O’Leary, D.D.M., 2004. EMX2 regulates sizes and positioning of the primary sensory and motor areas in neocortex by direct specification of cortical progenitors. Neuron 43, 359–372. Hanashima, C., Fernandes, M., Hebert, J.M., Fishell, G., 2007. The role of Foxg1 and dorsal midline signaling in the generation of Cajal-Retzius subtypes. J. Neurosci. 27, 11103–11111. 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. Haubensak, W., Attardo, A., Denk, W., Huttner, W.B., 2004. 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. Hill, R.S., Walsh, C.A., 2005. Molecular insights into human brain evolution. Nature 437, 64–67. Huang, X., Liu, J., Ketova, T., Fleming, J.T., Grover, V.K., Cooper, M.K., Litingtung, Y., Chiang, C., 2010. Transventricular delivery of Sonic hedgehog is essential to cerebellar ventricular zone development. Proc. Natl. Acad. Sci. U.S.A. 107, 8422–8427. Iacopetti, P., Michelini, M., Stuckmann, I., Oback, B., Aaku-Saraste, E., Huttner, W.B., 1999. Expression of the antiproliferative gene TIS21 at the onset of neurogenesis identifies single neuroepithelial cells that switch from proliferative to neurongenerating division. Proc. Natl. Acad. Sci. U.S.A. 96, 4639–4644. Jandial, R., Singec, I., Ames, C.P., Snyder, E.Y., 2008. Genetic modification of neural stem cells. Mol. Ther. J. Am. Soc. Gene Ther. 16, 450–457. ´ 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. Kahn, D.M., Krubitzer, L., 2002. Massive cross-modal cortical plasticity and the emergence of a new cortical area in developmentally blind mammals. Proc. Natl. Acad. Sci. U.S.A. 99, 11429–11434. Kang, H.J., Kawasawa, Y.I., Cheng, F., Zhu, Y., Xu, X., Li, M., Sousa, A.M.M., Pletikos, M., Meyer, K.A., Sedmak, G., Guennel, T., Shin, Y., Johnson, M.B., Krsnik, Z., Mayer, S., Fertuzinhos, S., Umlauf, S., Lisgo, S.N., Vortmeyer, A., Weinberger, D.R., Mane, S., Hyde, T.M., Huttner, A., Reimers, M., Kleinman, J.E., Sestan, N., 2011. Spatiotemporal transcriptome of the human brain. Nature 478, 483–489. Karlen, S.J., Kahn, D.M., Krubitzer, L., 2006. Early blindness results in abnormal corticocortical and thalamocortical connections. Neuroscience 142, 843–858. Krubitzer, L., 2007. The magnificent compromise: cortical field evolution in mammals. Neuron 56, 201–208. Krubitzer, L., Dooley, J.C., 2013. Cortical plasticity within and across lifetimes: how can development inform us about phenotypic transformations? Front. Hum. Neurosci. 7, 620. Krubitzer, L.A., Seelke, A.M.H., 2012. Cortical evolution in mammals: the bane and beauty of phenotypic variability. Proc. Natl. Acad. Sci. U.S.A. 109 (Suppl. 1), 10647–10654. Kumamoto, T., Toma, K., Gunadi, McKenna, W.L., Kasukawa, T., Katzman, S., Chen, B., Hanashima, C., 2013. Foxg1 coordinates the switch from nonradially to radially migrating glutamatergic subtypes in the neocortex through spatiotemporal repression. Cell Rep. 3, 931–945. Kwan, K.Y., Sestan, N., Anton, E.S., 2012. Transcriptional co-regulation of neuronal migration and laminar identity in the neocortex. Dev. Camb. Engl. 139, 1535–1546. LaMonica, B.E., Lui, J.H., Hansen, D.V., Kriegstein, A.R., 2013. Mitotic spindle orientation predicts outer radial glial cell generation in human neocortex. Nat. Commun. 4, 1665. Larsen, D.D., Krubitzer, L., 2008. Genetic and epigenetic contributions to the cortical phenotype in mammals. Brain Res. Bull. 75, 391–397. Lehtinen, M.K., Walsh, C.A., 2011. Neurogenesis at the brain-cerebrospinal fluid interface. Annu. Rev. Cell Dev. Biol. 27, 653–679. Lillien, L., Gulacsi, A., 2006. Environmental signals elicit multiple responses in dorsal telencephalic progenitors by threshold-dependent mechanisms. Cereb. Cortex (New York, N.Y.: 1991) 16 (Suppl. 1), i74–i81. Lukaszewicz, A., Savatier, P., Cortay, V., Giroud, P., Huissoud, C., Berland, M., Kennedy, H., Dehay, C., 2005. G1 phase regulation, area-specific cell cycle control, and cytoarchitectonics in the primate cortex. Neuron 47, 353–364. Mallamaci, A., Muzio, L., Chan, C.H., Parnavelas, J., Boncinelli, E., 2000. Area identity shifts in the early cerebral cortex of Emx2-/- mutant mice. Nat. Neurosci. 3, 679–686. McConnell, S.K., 1988. Fates of visual cortical neurons in the ferret after isochronic and heterochronic transplantation. J. Neurosci. 8, 945–974.

75

Meyer, G., 2010. Building a human cortex: the evolutionary differentiation of CajalRetzius cells and the cortical hem. J. Anat. 217, 334–343. Meyer, G., Goffinet, A.M., 1998. Prenatal development of reelin-immunoreactive neurons in the human neocortex. J. Comp. Neurol. 397, 29–40. Meyer, G., Perez-Garcia, C.G., Abraham, H., Caput, D., 2002. Expression of p73 and Reelin in the developing human cortex. J. Neurosci. 22, 4973–4986. Meyer, G., Soria, J.M., Martínez-Galán, J.R., Martín-Clemente, B., Fairén, A., 1998. Different origins and developmental histories of transient neurons in the marginal zone of the fetal and neonatal rat cortex. J. Comp. Neurol. 397, 493–518. 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. Dev. Camb. Engl. 131, 3133–3145. Molnár, Z., Métin, C., Stoykova, A., Tarabykin, V., Price, D.J., Francis, F., Meyer, G., Dehay, C., Kennedy, H., 2006. Comparative aspects of cerebral cortical development. Eur. J. Neurosci. 23, 921–934. Muzio, L., Mallamaci, A., 2005. Foxg1 confines Cajal-Retzius neuronogenesis and hippocampal morphogenesis to the dorsomedial pallium. J. Neurosci. 25, 4435–4441. Nakagawa, Y., Johnson, J.E., O’Leary, D.D., 1999. Graded and areal expression patterns of regulatory genes and cadherins in embryonic neocortex independent of thalamocortical input. J. Neurosci. 19, 10877–10885. Nishihara, H., Hasegawa, M., Okada, N., 2006. Pegasoferae, an unexpected mammalian clade revealed by tracking ancient retroposon insertions. Proc. Natl. Acad. Sci. U.S.A. 103, 9929–9934. ˜ 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. 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. O’Leary, D.D., 1989. Do cortical areas emerge from a protocortex? Trends Neurosci. 12, 400–406. O’Leary, D.D., Sahara, S., 2008. Genetic regulation of arealization of the neocortex. Curr. Opin. Neurobiol. 18, 90–100. O’Leary, D.D., Schlaggar, B.L., Tuttle, R., 1994. Specification of neocortical areas and thalamocortical connections. Annu. Rev. Neurosci. 17, 419–439. O’Leary, D.D.M., Chou, S.-J., Sahara, S., 2007. Area patterning of the mammalian cortex. Neuron 56, 252–269. Ogawa, M., Miyata, T., Nakajima, K., Yagyu, K., Seike, M., Ikenaka, K., Yamamoto, H., Mikoshiba, K., 1995. The reeler gene-associated antigen on Cajal-Retzius neurons is a crucial molecule for laminar organization of cortical neurons. Neuron 14, 899–912. Pearce, E., Stringer, C., Dunbar, R.I.M., 2013. New insights into differences in brain organization between Neanderthals and anatomically modern humans. Proc. Biol. Sci. 280, 20130168. Pierani, A., Wassef, M., 2009. Cerebral cortex development: From progenitors patterning to neocortical size during evolution. Dev. Growth Differ. 51, 325–342. Pilaz, L.-J., Patti, D., Marcy, G., Ollier, E., Pfister, S., Douglas, R.J., Betizeau, M., Gautier, E., Cortay, V., Doerflinger, N., Kennedy, H., Dehay, C., 2009. Forced G1-phase reduction alters mode of division, neuron number, and laminar phenotype in the cerebral cortex. Proc. Natl. Acad. Sci. U.S.A. 106, 21924–21929. 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., Dehay, C., Igel, H., Ares Jr., M., Vanderhaeghen, P., Haussler, D., 2006. An RNA gene expressed during cortical development evolved rapidly in humans. Nature 443, 167–172. Pouchelon, G., Gambino, F., Bellone, C., Telley, L., Vitali, I., Lüscher, C., Holtmaat, A., Jabaudon, D., 2014. Modality-specific thalamocortical inputs instruct the identity of postsynaptic L4 neurons. Nature, http://dx.doi.org/10.1038/nature13390 [Epub ahead of print]. Prabhakar, S., Noonan, J.P., Pääbo, S., Rubin, E.M., 2006. Accelerated evolution of conserved noncoding sequences in humans. Science 314, 786. Prüfer, K., Racimo, F., Patterson, N., Jay, F., Sankararaman, S., Sawyer, S., Heinze, A., Renaud, G., Sudmant, P.H., de Filippo, C., Li, H., Mallick, S., Dannemann, M., Fu, Q., Kircher, M., Kuhlwilm, M., Lachmann, M., Meyer, M., Ongyerth, M., Siebauer, M., Theunert, C., Tandon, A., Moorjani, P., Pickrell, J., Mullikin, J.C., Vohr, S.H., Green, R.E., Hellmann, I., Johnson, P.L.F., Blanche, H., Cann, H., Kitzman, J.O., Shendure, J., Eichler, E.E., Lein, E.S., Bakken, T.E., Golovanova, L.V., Doronichev, V.B., Shunkov, M.V., Derevianko, A.P., Viola, B., Slatkin, M., Reich, D., Kelso, J., Pääbo, S., 2014. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 505, 43–49. Raballo, R., Rhee, J., Lyn-Cook, R., Leckman, J.F., Schwartz, M.L., Vaccarino, F.M., 2000. Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex. J. Neurosci. 20, 5012–5023. Rakic, P., 1988. Specification of cerebral cortical areas. Science 241, 170–176. Rakic, P., 2009. Evolution of the neocortex: a perspective from developmental biology. Nat. Rev. Neurosci. 10, 724–735. ˜ Rakic, P., Suner, I., Williams, R.W., 1991. A novel cytoarchitectonic area induced experimentally within the primate visual cortex. Proc. Natl. Acad. Sci. U.S.A. 88, 2083–2087. Reillo, I., Borrell, V., 2012. Germinal zones in the developing cerebral cortex of ferret: ontogeny, cell cycle kinetics, and diversity of progenitors. Cereb. Cortex (New York, N.Y.: 1991) 22, 2039–2054. Reillo, I., de Juan Romero, C., García-Cabezas, M.Á., Borrell, V., 2011. A role for intermediate radial glia in the tangential expansion of the mammalian cerebral cortex. Cereb. Cortex (New York, N.Y.: 1991) 21, 1674–1694.

76

Y. Arai, A. Pierani / Neuroscience Research 86 (2014) 66–76

Roy, A., Gonzalez-Gomez, M., Pierani, A., Meyer, G., Tole, S., 2014. Lhx2 regulates the development of the forebrain hem system. Cereb. Cortex (New York, N.Y.: 1991) 24, 1361–1372. Shimamura, K., Hartigan, D.J., Martinez, S., Puelles, L., Rubenstein, J.L., 1995. Longitudinal organization of the anterior neural plate and neural tube. Dev. Camb. Engl. 121, 3923–3933. Shimogori, T., Banuchi, V., Ng, H.Y., Strauss, J.B., Grove, E.A., 2004. Embryonic signaling centers expressing BMP, WNT and FGF proteins interact to pattern the cerebral cortex. Dev. Camb. Engl. 131, 5639–5647. 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. Shitamukai, A., Matsuzaki, F., 2012. Control of asymmetric cell division of mammalian neural progenitors. Dev. Growth Differ. 54, 277–286. Siegenthaler, J.A., Miller, M.W., 2008. Generation of Cajal-Retzius neurons in mouse forebrain is regulated by transforming growth factor beta-Fox signaling pathways. Dev. Biol. 313, 35–46. Smart, I.H.M., Dehay, C., Giroud, P., Berland, M., Kennedy, H., 2002. Unique morphological features of the proliferative zones and postmitotic compartments of the neural epithelium giving rise to striate and extrastriate cortex in the monkey. Cereb. Cortex (New York, N.Y.: 1991) 12, 37–53. Takahashi, T., Nowakowski, R.S., Caviness Jr., V.S., 1995. The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall. J. Neurosci. 15, 6046–6057. Takiguchi-Hayashi, K., Sekiguchi, M., Ashigaki, S., Takamatsu, M., Hasegawa, H., Suzuki-Migishima, R., Yokoyama, M., Nakanishi, S., Tanabe, Y., 2004. Generation of reelin-positive marginal zone cells from the caudomedial wall of telencephalic vesicles. J. Neurosci. 24, 2286–2295. Tissir, F., Ravni, A., Achouri, Y., Riethmacher, D., Meyer, G., Goffinet, A.M., 2009. DeltaNp73 regulates neuronal survival in vivo. Proc. Natl. Acad. Sci. U.S.A. 106, 16871–16876.

Toyoda, R., Assimacopoulos, S., Wilcoxon, J., Taylor, A., Feldman, P., Suzuki-Hirano, A., Shimogori, T., Grove, E.A., 2010. FGF8 acts as a classic diffusible morphogen to pattern the neocortex. Dev. Camb. Engl. 137, 3439–3448. Vaccarino, F.M., Schwartz, M.L., Raballo, R., Rhee, J., Lyn-Cook, R., 1999. Fibroblast growth factor signaling regulates growth and morphogenesis at multiple steps during brain development. Curr. Top. Dev. Biol. 46, 179–200. Van Pelt, J., Uylings, H.B.M., 2002. Branching rates and growth functions in the outgrowth of dendritic branching patterns. Network (Bristol, England) 13, 261–281. Viti, J., Gulacsi, A., Lillien, L., 2003. Wnt regulation of progenitor maturation in the cortex depends on Shh or fibroblast growth factor 2. J. Neurosci. 23, 5919–5927. Vue, T.Y., Lee, M., Tan, Y.E., Werkhoven, Z., Wang, L., Nakagawa, Y., 2013. Thalamic control of neocortical area formation in mice. J. Neurosci. 33, 8442– 8453. Wang, X., Tsai, J.-W., LaMonica, B., Kriegstein, A.R., 2011. A new subtype of progenitor cell in the mouse embryonic neocortex. Nat. Neurosci. 14, 555– 561. Yang, A., McKeon, F., 2000. P63 and P73: P53 mimics, menaces and more. Nat. Rev. Mol. Cell Biol. 1, 199–207. Yoshida, M., Assimacopoulos, S., Jones, K.R., Grove, E.A., 2006. Massive loss of CajalRetzius cells does not disrupt neocortical layer order. Dev. Camb. Engl. 133, 537–545. Zecevic, N., Rakic, P., 2001. Development of layer I neurons in the primate cerebral cortex. J. Neurosci. 21, 5607–5619. Zembrzycki, A., Griesel, G., Stoykova, A., Mansouri, A., 2007. Genetic interplay between the transcription factors Sp8 and Emx2 in the patterning of the forebrain. Neural Dev. 2, 8. Zimmer, C., Lee, J., Griveau, A., Arber, S., Pierani, A., Garel, S., Guillemot, F., 2010. Role of Fgf8 signalling in the specification of rostral Cajal-Retzius cells. Dev. Camb. Engl. 137, 293–302.