The neural crest (NC) is an embryonic cell population that contributes to key vertebrate-specific features including the craniofacial skeleton and peripheral nervous system. Here we examine the transcriptional and epigenomic profiles of NC cells in the sea lamprey, in order to gain insight into the ancestral state of the NC gene regulatory network (GRN). Transcriptome analyses identify clusters of co-regulated genes during NC specification and migration that show high conservation across vertebrates but also identify transcription factors (TFs) and cell-adhesion molecules not previously implicated in NC migration. ATAC-seq analysis uncovers an ensemble of cis-regulatory elements, including enhancers of Tfap2B, SoxE1 and Hox-α2 validated in the embryo. Cross-species deployment of lamprey elements identifies the deep conservation of lamprey SoxE1 enhancer activity, mediating homologous expression in jawed vertebrates. Our data provide insight into the core GRN elements conserved to the base of the vertebrates and expose others that are unique to lampreys.

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Published in Nature Communications, v. 10, article no. 4689.

© The Author(s) 2019

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.

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This work was supported by a Leverhulme Research Grant to T.S.S. (RPG-2015–026), the National Institute of General Medical Sciences of the National Institutes of Health grants to J.J.S. (R01GM104123) and C.T.A. (R24GM095471), a Wellcome Trust Institutional Strategic Support Fund grant (H2RZKC00) to D.H. and T.S.S., a Junior Research Fellowship (Trinity College, Oxford), the Sydney Brenner Fellowship, a Company of Biologists Travelling Fellowship (DEVTF-150403) and an EMBO Short Term Fellowship to D.H., and a Clarendon Fund Fellowship to V.C.M.

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The authors declare that all data supporting the findings of this study are available within the article and its supplementary information files or from the corresponding author upon reasonable request. The data sets generated during and/or analysed during the current study have been deposited in the NCBI GEOarchive database under accession code: GSE112072 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112072.

The custom script used to calculate motif co-occurrences is available at https://github.com/tsslab/chick_NC-GRN. Details of software versions and parameters used, when different from default, are indicated in the Methods section.

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Reporting summary

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