Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Division of Cell Biology, Department of Human Biology, Neuroscience Institute, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Nat Commun. 2019 Oct 16;10(1):4689. doi: 10.1038/s41467-019-12687-4.
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.
神经嵴(NC)是一种胚胎细胞群体,它有助于形成关键的脊椎动物特征,包括颅面骨骼和周围神经系统。在这里,我们研究了七鳃鳗的 NC 细胞的转录组和表观基因组图谱,以便深入了解 NC 基因调控网络(GRN)的祖先进化状态。转录组分析在 NC 特化和迁移过程中识别出了一组共同调节的基因簇,这些基因在脊椎动物中具有高度保守性,但也鉴定出了先前与 NC 迁移无关的转录因子(TFs)和细胞黏附分子。ATAC-seq 分析揭示了一套顺式调控元件,包括 Tfap2B、SoxE1 和 Hox-α2 的增强子,这些增强子在胚胎中得到了验证。七鳃鳗元件在跨物种中的应用鉴定出了七鳃鳗 SoxE1 增强子活性的深度保守性,介导了有颌脊椎动物的同源表达。我们的数据为深入了解脊椎动物基部保守的核心 GRN 元件提供了线索,并揭示了其他仅存在于七鳃鳗中的独特元件。