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

Abstract

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-α2 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.

Combinatorial chromatin dynamics foster accurate cardiopharyngeal fate choices

“…S1). General metrics including peak numbers, size, GC content and genomic distribution were comparable to consensus peaksets reported in similar studies of chromatin accessibility in developmental contexts [19][20][21][22][23] (Supplementary text; Fig. S1).…”

Evolutionary and Developmental Associations of Neural Crest and Placodes in the Vertebrate Head: Insights From Jawless Vertebrates

“…The neural crest GRN is a spatial and temporal continuum of gene regulatory interactions from start to finish, and cannot therefore, be broken down into completely separable units for each stage of development. We can, however, recognize and study unique GRN “subcircuits”—a set of common gene regulatory interactions that govern similar mechanisms of neural crest development across highly divergent groups (e.g., mouse and fish; Meulemans and Bronner-Fraser, 2004 ; Sauka-Spengler et al, 2007 ; Simões-Costa and Bronner, 2015 ; Hockman et al, 2019 ; Parker et al, 2019 ).…”

“…This owes largely to the fact that lamprey adults and their embryos are relatively easy to obtain and rear in simple laboratory settings, at least compared to hagfish ( York et al, 2019a ; described below). Moreover, accessibility to annotated genomes and transcriptomes, as well as the application of modern molecular genetic techniques such as cell lineage tracing, overexpression of DNAs and RNAs, and knockdown/knockout experiments such as morpholinos and CRISPR/Cas9 genome editing has allowed researchers to address long-standing hypotheses concerning the origin and evolution of vertebrate traits, including neural crest and placodes ( McCauley and Bronner-Fraser, 2006 ; Smith et al, 2013 , 2018 ; Parker et al, 2014 ; Square et al, 2015 ; Zu et al, 2016 ; Hockman et al, 2019 ; York et al, 2019a ; York and McCauley, 2020a ).…”

“…These similarities extend beyond expression patterns. Studies involving gene knockdown/knockout, enhancer analysis, and chromatin profiling have revealed that many of the regulatory interactions at multiple tiers in the neural crest GRN are also shared between lampreys and jawed vertebrates ( Sauka-Spengler et al, 2007 ; Nikitina et al, 2008 ; Lakiza et al, 2011 ; York et al, 2017 , 2018 , 2019b ; Hockman et al, 2019 ; Parker et al, 2019 ; Yuan et al, 2020 ). There is also evidence that the production of several neural crest cell types shared between lampreys and jawed vertebrates relies upon a common gene regulatory logic.…”

An atlas of neural crest lineages along the posterior developing zebrafish at single-cell resolution

“…During their development, NCCs undergo dramatic transcriptional changes which lead to diverse cellular lineages, making their transcriptomic profiles highly dynamic (Simões-Costa et al, 2014;Martik et al, 2017;Soldatov et al, 2019;Williams et al, 2019). In support of the model that complex transcriptional programs govern NCC ontogenesis, gene regulatory networks involved in early development of NCCs into broad cell types has been studied at a high level using a combination of transcriptomics, chromatin profiling and enhancer studies, especially during pre-migratory and early migratory NCC specification along cranial axial regions, across amniotes (Martik et al, 2017;Simoes-Costa and Bronner, 2016;Green et al 2016;Lumb et al, 2017;Williams et al, 2019;Hockman et al, 2019). For example, during premigratory stages the transcription factors FoxD3, Tfap2a and Sox9 are important for NCC fate specification and in turn regulate the expression of Sox10, a conserved transcription factor that is expressed along all axial levels by early migrating NCCs and within many differentiating lineages (Sauka-Spengler and Bronner-Fraser, 2008;Martik et al, 2017).…”