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Ancient deuterostome origins of vertebrate brain signalling centres

Abstract

Neuroectodermal signalling centres induce and pattern many novel vertebrate brain structures but are absent, or divergent, in invertebrate chordates. This has led to the idea that signalling-centre genetic programs were first assembled in stem vertebrates and potentially drove morphological innovations of the brain. However, this scenario presumes that extant cephalochordates accurately represent ancestral chordate characters, which has not been tested using close chordate outgroups. Here we report that genetic programs homologous to three vertebrate signalling centresthe anterior neural ridge, zona limitans intrathalamica and isthmic organizerare present in the hemichordate Saccoglossus kowalevskii. Fgf8/17/18 (a single gene homologous to vertebrate Fgf8, Fgf17 and Fgf18), sfrp1/5, hh and wnt1 are expressed in vertebrate-like arrangements in hemichordate ectoderm, and homologous genetic mechanisms regulate ectodermal patterning in both animals. We propose that these genetic programs were components of an unexpectedly complex, ancient genetic regulatory scaffold for deuterostome body patterning that degenerated in amphioxus and ascidians, but was retained to pattern divergent structures in hemichordates and vertebrates.

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Figure 1: An ANR-like signalling centre in S. kowalevskii.
Figure 2: A ZLI-like signalling centre in S. kowalevskii.
Figure 3: An IsO-like signalling centre in S. kowalevskii.
Figure 4: Evolutionary gain and loss of ANR, ZLI and IsO-like genetic programs.

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Data deposits

S. kowalevskii gene sequences have been deposited in GenBank, and accession numbers are provided in Supplementary Table 2.

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Acknowledgements

We thank J. Gerhart and M. Kirschner for assistance and support, R. Freeman for bioinformatics assistance, E. Farrelly, M. Terasaki and S. Darras for technical guidance, the members of the Lowe laboratory for discussions, and G. Wray and J. Gerhart for comments on drafts of the manuscript. We also thank the staff of the Marine Biological Laboratory, the Waquoit Bay National Estuarine Research Reserve, Carl Zeiss and Nikon for assistance during our field season. This work was funded by the Searle Kinship Foundation, Brain Research Foundation and National Science Foundation grant 1049106 (C.J.L.), National Institutes of Health grant R01 HD42330 (E.A.G.) and the University of Chicago Hinds Fund (A.M.P). A.M.P. was supported by a Marine Biological Laboratory Frank R. Lillie Fellowship, National Institute of Child Health and Development institutional training grant 1T32HD055164-01A1, and National Institute of Neurological Disorders and Stroke pre-doctoral fellowship 1F31NS074738-01A1. J.A. was supported by a National Science and Engineering Research Council of Canada pre-doctoral grant.

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A.M.P., C.J.L. and J.A. conceived the project. A.M.P. and C.J.L. performed the hemichordate experiments and wrote the paper. E.E.M. and S.A. performed mouse experiments, and E.A.G. edited the paper. All authors discussed and commented on the data.

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Correspondence to Christopher J. Lowe.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-4 and Supplementary Tables 1-2. Please note that Supplementary Figure 1 shows that fz5/8 siRNA affects proboscis patterning specifically and that Supplementary Figure 2 shows Ptch expression in wild-type S. kowalevskii embryos and spectrum of phenotypes after hh siRNA injection. Ptch expression indicates that hh can signal to numerous body regions. Hh siRNA injection causes pleiotropic effects on AP and DV patterning. (PDF 2369 kb)

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Pani, A., Mullarkey, E., Aronowicz, J. et al. Ancient deuterostome origins of vertebrate brain signalling centres. Nature 483, 289–294 (2012). https://doi.org/10.1038/nature10838

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