Animal Evolution: Convergent Nerve Cords?

Current Biology

Dispatches Animal Evolution: Convergent Nerve Cords? Detlev Arendt EMBL, Heidelberg, Germany Correspondence: [email protected] https://doi.org/10.1016/j.cub.2018.01.056

How the centralized nervous systems of animals evolved remains unclear. Do the nerve cords found at various positions in the worm-shaped bodies of bilaterian animals have a common or an independent evolutionary origin? New comparative data fuel this long-standing debate. Centralized nervous systems involve the clustering of neurons and bundling of axons. For example, a pair of nerve cords of variable thickness and mediolateral position is found on the ventral side in almost all lophotrochozoans (the animal superphylum including molluscs and annelids) and ecdysozoans (the superphylum including arthropods and nematodes) (Figure 1) [1]. In chordates, by contrast, the neural tube emerges dorsally from a condensation of neurons and axons. An exciting question in animal evolution is whether invertebrate nerve cords and vertebrate neural tube can be traced back to a common centralized structure, or whether they evolved  independently. In a recent paper [2], Jose Marı´a Martı´n-Dura´n and colleagues in the laboratory of Andreas Hejnol have addressed this question by comparing gene expression in the developing nervous system of various invertebrates. Previous work had shown that the neuroectoderm — the tissue giving rise to the neural tube in vertebrates and the ventral nerve cords in invertebrates — forms topologically on the same side of the dorsoventral body axis with regard to BMP signaling, which establishes dorsoventral polarity in bilaterian animals [3–5]. The neuroectoderm will form wherever BMP signaling is lowest — the ventral side in invertebrates and the dorsal side in vertebrates. In addition, staggered expression of conserved transcription factors patterns the neuroectoderm in annelids and vertebrates from medial to lateral, giving rise to different subpopulations of neurons (Figure 1 B,C) [3]. This suggests that similar neurogenic regions already existed in the ancestor of all bilaterian animals. To test this hypothesis further, Martı´nDura´n and colleagues [2] now provide important new gene expression data for

five lophotrochozoan species (Figure 1A), including an annelid, two brachiopods (lampshells), a nemertean (ribbon worm), a rotifer (wheel animal); and for two acoelomorph species — minute, flatwormlike worms with a blind-ended gut. Martı´nDura´n and colleagues [2] report that mediolateral neuroectoderm patterning, as previously uncovered for the annelid Platynereis [3], seems to be largely absent from the annelid Owenia fusiformis. Moreover, they find that mediolateral patterning is similar in the two brachiopod species and in the ribbon worm, but is virtually absent in the rotifer and highly variable in acoelomorphs. The authors interpret these findings as evidence that nerve cords and mediolateral patterning evolved independently in several lineages of bilaterian animals [2]. This interpretation has dramatic consequences for our understanding of nervous system evolution, because the nerve cords patterned by these genes would have to be regarded as independent evolutionary acquisitions. According to this scenario, the bilaterian ancestor would have possessed only a diffuse nerve net, and centralized nerve cords would have emerged multiple times independently and at different positions (dorsally or ventrally) in the body. There are, however, several problems with this interpretation: for one, absence of evidence is not evidence of absence. To draw firm conclusions, for example, all relevant development stages should be considered. Unfortunately, this was not the case for Owenia, where the nervecord-forming stages [6] are not covered. Martı´n-Dura´n and colleagues [2] only investigated earlier larval and later juvenile stages when the nerve cord is long developed. Moreover, for species where appropriate developmental stages are covered — for example brachiopods

and ribbon worms — considerable similarities in nerve cord mediolateral patterning are apparent from the new data (Figure 1 D,F) that appear entirely consistent with the alternative hypothesis, namely that mediolateral nerve cord patterning is evolutionarily ancient and persisted, in multiple variants, in modern animals. Supporting this notion, adult brachiopods are sedentary animals with a crown of tentacles and a highly modified body protected by shells. Their larvae transitorily resemble young annelid worms, with lateral pairs of bristles and rudimentary ventral nerve cords. For these larval stages, Martı´n-Duran and colleagues [2] now document a modified variant of Platynereis-type mediolateral patterning [1] (Figure 1D). The reported absence of cholinergic motor neurons in the brachiopod larval trunk [2] may represent an evolutionary adaptation to the sedentary lifestyle and loss of wormlike locomotion. Likewise, the peculiar ribbon worms with their highly plastic, flattened body do show pronounced mediolateral patterning of the neuroectoderm [2] (Figure 1F). In recent phylogenies [7], ribbon worms emerge as a sister to a group comprising annelids, molluscs and brachiopods (Figure 1), which makes them especially relevant for understanding ancestral conditions for this group (Figure 1). Interestingly, their ventral nerve cords develop in a very lateral position, while in between the cords there is a mucociliary sole that secretes and transports mucus via ciliary beating and allows them to glide slowly on a trail of slime. Such mucociliary soles are found in other lophotrochozoans and xenacoelomorphs, and have been proposed to represent an ancient bilaterian condition [8]. The new ribbon worm data [2] thus suggest that the

Current Biology 28, R208–R231, March 5, 2018 ª 2018 Elsevier Ltd. R225

Current Biology

Dispatches A

l

Chordata msx pax3/7 pax6

nk6 nkx2.1/2 foxA

Vertebrata

Xenopus

Tunicata

Ciona

Acrania

i m B 5HT ACh ?

Xenopus

Branchiostoma

C

Ambulacraria Hemichordata Balanoglossus

? ? ?

5HT ACh

Echinodermata Patiria Lophotrochozoa

Platynereis PPlatynereis Pla t reis tyne r

D

Platynereis P

Annelida

?

5HT

Owenia* O

? Terebratalia

Brachiopoda

Terebratalia* T

E ?

Novocrania* N

Sepia

Mollusca

Sepia

Nemertini

Lineus*

? ?

Platyhelminthes Schmidtea

Gnathifera

?

Epiphanes*

F

?

5HT ACh

?

*

* ?

Lineus

?

G

?

Ecdysozoa

Priapulida

Priapulus

5HT ACh

?

Schmidtea

Nematoda Caenorhabditis Arthropoda Drosophila

Xenacoelomorpha

IIsodiametra* M Meara*

?

Cnidaria

Nematostella

?

H

?

?

?

Drosophila

I

?

?

Nematostella

Current Biology

Figure 1. The evolution of mediolateral patterning in bilaterian neuroectoderm. (A) Evolutionary tree of the bilaterian animals [7] with cnidarians as an outgroup. Available gene expression data for mediolateral neuroectodermal patterning depicted for representative species. Species names in bold indicate datasets on which initial comparisons were based. Asterisks indicate species included in [2]. Grey oval outline marks species not adequately included in [2] but of importance for parsimony reconstruction of ancestral state. For references see text; for nematodes and amphioxus see [18] and [19]. Mediolateral patterning schemes at basal nodes of the tree represent hypothetical ancestral states. Abbreviations: l, lateral; i, intermediate; m, medial neurogenic region. Question marks in mediolateral patterning indicate missing data. Dashes indicate no role in mediolateral patterning. Dashed line for Xenacoelomorpha reflects unclear phylogenetic placement.) (B–I) Conserved aspects of mediolateral patterning in representative bilaterians and in the cnidarian outgroup. 5HT and Ach indicate differentiation of serotoninergic and cholinergic neurons from medial and intermediate columns, respectively. (B) Mediolateral patterning in Xenopus laevis neurula after [15]; (C) in the 2-dayold trochophora larva of the annelid Platynereis dumerilii after [3]; (D) in the brachiopod Terebratalia after [2]; (E) in the mollusk cephalopod Sepia officinalis after [9]; (F) in the ribbon worm Lineus ruber after [2]; (G) in the flatworm Schmidtea mediterranea after [10–12] (*data for Dugesia [20]); (H) in Drosophila melanogaster gnathal segments after [16]; (I) and in the sea anemone Nematostella vectensis after a compilation of data in [14].

medial column may have ancestrally given rise to serotonergic neurons embedded in the mucociliary sole, and the intermediate column to cholinergic motor neurons in the adjacent ventrolateral nerve cords. Nonetheless, Martı´n-Duran and colleagues [2] argue that mediolateral

nerve cord patterning was absent in the ancestral lophotrochozoan. Importantly, they ignore recent studies on molluscs and flatworms, key phyla for inferring the ancestral state of lophotrochozoans (Figure 1A) [7]. Indeed, a full, staggered pattern of conserved mediolateral genes has been reported in the cuttlefish Sepia

R226 Current Biology 28, R208–R231, March 5, 2018

officinalis (Figure 1E) [9], and recent studies in the flatworm Schmidtea mediterranea (Figure 1G) indicate the presence of conserved mediolateral regions producing cholinergic and medial serotonergic neurons [10–12]. This is in direct conflict with the view of Dura´n and colleagues [2] that in the flatworm neuroectoderm dorsoventral patterning is absent. How about bilaterians as a whole? Here, the ancestral state of neuroectoderm patterning is more ambiguous, because mediolateral patterns appear to be missing in important branches (Figure 1A), such as sea stars (Figure 1A), or highly divergent, as in acorn worms [13]. Adding to this, Martı´n-Dura´n and colleagues [2] report a limited and variable extent of mediolateral patterning in Isodiametra pulchra and Meara stichopi, two groups of acoelomorph that are considered sister groups to all other bilaterian animals (Figure 1A). This may reflect the ancestral bilaterian state or, alternatively, be due to a later loss in these lineages. Supporting the latter, a full staggered sequence of conserved mediolateral transcription factors is present in a cnidarian, a bilaterian outgroup (Figure 1H) [14]. So what is the state of the debate on convergent nerve cords? Following the principle of evolutionary parsimony (Figure 1A), conservation of mediolateral patterning appears very clear across lophotrochozoans, convincing across protostomes, and still likely across bilaterian animals. Adding to this, available data for frogs [15], annelids [3], and flies [16] and the new data for brachiopods [2], ribbon worms [2], molluscs [9] and flatworms [10,11] support, rather than defy, an ancient role of mediolateral patterning in nerve cord formation (Figure 1B– H). For sea stars, acorn worms, and acoelomorphs, this link is less clear, as advocated by Martı´nDura´n and colleagues [2]. In any case, it must be stressed that the homology of nerve cords in these groups is far from proven. As very little is known about the distinct neuron types that the conserved neurogenic regions produce in the different groups of animals, no firm statement can yet be made about the cellular neural architecture of ancient ecdysozoans, lophotrochozoans, or bilaterians. Did mediolateral serotonergic, cholinergic and sensory neurons form

Current Biology

Dispatches part of nerve cords or of an elaborate nerve net as found in cnidarians and some bilaterians? Clearly, we need to know more about the diversity and specific characteristics of the neuron types emerging from mediolateral regions in the various groups. Encouragingly, this may be accomplished in the near future by a large set of comparative transcriptomics datasets that are currently beginning to appear [17]. With these, clarity might finally emerge in the exciting, centurylong debate on nerve cord homology. REFERENCES 1. Nielsen, C. (2012). Animal Evolution. Interrelationships of the Living Phyla, 3 Edition (Oxford: Oxford University press). 2. Martin-Duran, J.M., Pang, K., Borve, A., Le, H.S., Furu, A., Cannon, J.T., Jondelius, U., and Hejnol, A. (2018). Convergent evolution of bilaterian nerve cords. Nature 553, 45–50. 3. Denes, A.S., Jekely, G., Steinmetz, P.R., Raible, F., Snyman, H., Prud’homme, B., Ferrier, D.E., Balavoine, G., and Arendt, D. (2007). Molecular architecture of annelid nerve cord supports common origin of nervous system centralization in bilateria. Cell 129, 277–288. 4. Holley, S.A., Jackson, P.D., Sasai, Y., Lu, B., De Robertis, E.M., Hoffmann, F.M., and Ferguson, E.L. (1995). A conserved system for dorsal-ventral patterning in insects and vertebrates involving sog and chordin [see comments]. Nature 376, 249–253. 5. Arendt, D., and Nu¨bler-Jung, K. (1994). Inversion of dorsoventral axis? Nature 371, 26.

6. Helm, C., Vocking, O., Kourtesis, I., and Hausen, H. (2016). Owenia fusiformis - a basally branching annelid suitable for studying ancestral features of annelid neural development. BMC Evol. Biol. 16, 129. 7. Kocot, K.M., Struck, T.H., Merkel, J., Waits, D.S., Todt, C., Brannock, P.M., Weese, D.A., Cannon, J.T., Moroz, L.L., Lieb, B., et al. (2017). Phylogenomics of Lophotrochozoa with consideration of systematic error. Syst. Biol. 66, 256–282. 8. Arendt, D., Benito-Gutierrez, E., Brunet, T., and Marlow, H. (2015). Gastric pouches and the mucociliary sole: setting the stage for nervous system evolution. Philos. Trans. R. Soc. Lond. B Biol. Sci. 370. 9. Buresi, A., Andouche, A., Navet, S., Bassaglia, Y., Bonnaud-Ponticelli, L., and Baratte, S. (2016). Nervous system development in cephalopods: How egg yolk-richness modifies the topology of the mediolateral patterning system. Dev. Biol. 415, 143–156. 10. Wang, I.E., Lapan, S.W., Scimone, M.L., Clandinin, T.R., and Reddien, P.W. (2016). Hedgehog signaling regulates gene expression in planarian glia. Elife 5, e16996. 11. Scimone, M.L., Kravarik, K.M., Lapan, S.W., and Reddien, P.W. (2014). Neoblast specialization in regeneration of the planarian Schmidtea mediterranea. Stem Cell Rep. 3, 339–352. 12. Fraguas, S., Barberan, S., Ibarra, B., Stoger, L., and Cebria, F. (2012). Regeneration of neuronal cell types in Schmidtea mediterranea: an immunohistochemical and expression study. Int. J. Dev. Biol. 56, 143–153. 13. Kaul-Strehlow, S., Urata, M., Praher, D., and Wanninger, A. (2017). Neuronal patterning of the tubular collar cord is highly conserved among enteropneusts but dissimilar to the chordate neural tube. Sci. Rep. 7, 7003.

14. Arendt, D., Tosches, M.A., and Marlow, H. (2015). From nerve net to nerve ring, nerve cord and brain - evolution of the nervous system. Nat. Rev. Neurosci. 17, 61–72. 15. Dichmann, D.S., and Harland, R.M. (2010). Nkx6 genes pattern the frog neural plate and Nkx6.1 is necessary for motoneuron axon projection. Dev. Biol. 349, 378–386. 16. Urbach, R., Jussen, D., and Technau, G.M. (2016). Gene expression profiles uncover individual identities of gnathal neuroblasts and serial homologies in the embryonic CNS of Drosophila. Development 143, 1290–1301. 17. Vergara, H.M., Bertucci, P.Y., Hantz, P., Tosches, M.A., Achim, K., Vopalensky, P., and Arendt, D. (2017). Whole-organism cellular gene-expression atlas reveals conserved cell types in the ventral nerve cord of Platynereis dumerilii. Proc. Natl. Acad. Sci. USA 114, 5878–5885. 18. Albuixech-Crespo, B., Lopez-Blanch, L., Burguera, D., Maeso, I., Sanchez-Arrones, L., Moreno-Bravo, J.A., Somorjai, I., PascualAnaya, J., Puelles, E., Bovolenta, P., et al. (2017). Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain. PLoS Biol. 15, e2001573. 19. Li, Y., Zhao, D., Horie, T., Chen, G., Bao, H., Chen, S., Liu, W., Horie, R., Liang, T., Dong, B., et al. (2017). Conserved gene regulatory module specifies lateral neural borders across bilaterians. Proc. Natl. Acad. Sci. USA 114, E6352–E6360. 20. Mannini, L., Deri, P., Gremigni, V., Rossi, L., Salvetti, A., and Batistoni, R. (2008). Two msh/ msx-related genes, Djmsh1 and Djmsh2, contribute to the early blastema growth during planarian head regeneration. Int. J. Dev. Biol. 52, 943–952.

Neuroscience: An Olfactory Homunculus in the Insect Brain C. Giovanni Galizia Department of Neuroscience, University of Konstanz, 78457 Konstanz, Germany Correspondence: [email protected] https://doi.org/10.1016/j.cub.2018.01.058

Animals can follow olfactory traces to find food, detect a sexual mate, or avoid predators. A new study reveals that pheromone-specific projection neurons in the cockroach have a spatially tuned receptive field, and allow encoding spatial information of an odorant. The central nervous system relies on external inputs to generate an internal representation of the surrounding

environment. When I look outside my office’s window, the reflected sunlight hits the retina with a certain pattern of

colors and intensities. This complex stimulus is projected onto the visual cortex, allowing encoding of the spatial

Current Biology 28, R208–R231, March 5, 2018 ª 2018 Elsevier Ltd. R227