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

The neural crest 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 profiles and chromatin accessibility of neural crest cells in the basal sea lamprey, in order to gain insight into the ancestral state of the neural crest gene regulatory network (GRN) at the dawn of vertebrates. Transcriptome analyses reveal clusters of co-regulated genes during neural crest specification and migration that show high conservation across vertebrates for dynamic programmes like Wnt modulation during the epithelial to mesenchymal transition, but also reveal novel transcription factors and cell-adhesion molecules not previously implicated in neural crest migration. ATAC-seq analysis refines the location of known cis-regulatory elements at the Hox-a2 locus and uncovers novel cis-regulatory elements for Tfap2B and SoxE1. Moreover, cross-species deployment of lamprey elements in zebrafish reveals that the lamprey SoxE1 enhancer activity is deeply conserved, mediating homologous expression in jawed vertebrates. Together, our data provide new insight into the core elements of the GRN that are conserved to the base of the vertebrates, as well as expose elements that are unique to lampreys. Overall design: RNA-seq datasets from Tahara stage (T)18 (3 replicates), T20 (2 replicates) and T21 (3 replicates) dissected lamprey (P. marinus) dorsal neural tubes, count table generated with featureCounts, normalised count table generated with DESeq2. Dissected T20 lamprey (P. marinus) head (2 replicates) and whole embryo (2 replicates) RNA-seq datasets which have been merged. Transcriptome from dorsal neural tube, head and embryo RNA-seq datasets generated with cufflinks/cuffmerge. ATAC-seq datasets from T20 (3 replicates) and T21 (3 replicates) dissected lamprey (P. marinus) dorsal neural tubes, and T23 (3 replicates) dissected lamprey (P. marinus) heads. Consensus lamprey (P. marinus) ATAC-seq peakset, from peaks called by MACS2. ATAC-seq datasets from T20 (3 replicates) and T21 (4 replicates) dissected lamprey (L. planeri) dorsal neural tubes, and T23 (3 replicates) dissected lamprey (L. planeri) heads. Consensus lamprey (L. planeri) ATAC-seq peakset, from peaks called by MACS2.

9

Hockman D, Chong-Morrison V, Green SA, Gavriouchkina D, Candido-Ferreira I, Ling ITC, Williams RM, Amemiya CT, Smith JJ, Bronner ME, Sauka-Spengler T