A genome-wide assessment of the ancestral neural crest gene regulatory network

Dorit Hockman,Ivan Candido-Ferreira,Irving T C Ling,Chris T Amemiya,Marianne E Bronner,Vanessa Chong-Morrison,Tatjana Sauka-Spengler,Ruth M Williams,Daria Gavriouchkina,Stephen A Green,Jeramiah J Smith

doi:10.1038/s41467-019-12687-4

Abstract

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.

Highlights

The neural crest (NC) is an embryonic cell population that contributes to key vertebratespecific features including the craniofacial skeleton and peripheral nervous system
These results suggested that the basic NC gene regulatory network (GRN) was already present at the base of vertebrates, some key regulators were missing from the lamprey NC specifier module[7]
NC cells reside within the neural folds, which converge at T18 to form a neural rod and fuse at T20, when the first signs of NC migration have been reported[16,17]

Summary

Introduction

The neural crest (NC) is an embryonic cell population that contributes to key vertebratespecific features including the craniofacial skeleton and peripheral nervous system. By taking a candidate gene approach to compare lamprey and gnathostome TFs and signalling molecules, we previously showed that many key NC genes were conserved in expression and function between lamprey and jawed vertebrates[7]. These results suggested that the basic NC GRN was already present at the base of vertebrates, some key regulators were missing from the lamprey NC specifier module[7]. We identify enhancer elements that drive expression in the lamprey NC, and provide evidence that regulation of a SoxE family gene is conserved between jawless and jawed vertebrates. By adapting highthroughput tools to the lamprey, our data provide insight into the ancestral state of the NC GRN

Methods

Results

Conclusion