神经嵴
生物
神经板
神经形成
神经褶
外胚层
人口
颅神经嵴
神经管
神经科学
原肠化
遗传学
胚胎
胚胎发生
人口学
社会学
作者
Aleksandr Kotov,Subham Seal,Mansour Alkobtawi,Vincent Kappès,Sofia Medina Ruiz,Hugo Arbès,Richard M. Harland,Leonid Peshkin,Anne H. Monsoro-Burq
标识
DOI:10.1073/pnas.2311685121
摘要
Neural crest cells exemplify cellular diversification from a multipotent progenitor population. However, the full sequence of early molecular choices orchestrating the emergence of neural crest heterogeneity from the embryonic ectoderm remains elusive. Gene-regulatory-networks (GRN) govern early development and cell specification toward definitive neural crest. Here, we combine ultradense single-cell transcriptomes with machine-learning and large-scale transcriptomic and epigenomic experimental validation of selected trajectories, to provide the general principles and highlight specific features of the GRN underlying neural crest fate diversification from induction to early migration stages using Xenopus frog embryos as a model. During gastrulation, a transient neural border zone state precedes the choice between neural crest and placodes which includes multiple converging gene programs. During neurulation, transcription factor connectome, and bifurcation analyses demonstrate the early emergence of neural crest fates at the neural plate stage, alongside an unbiased multipotent-like lineage persisting until epithelial–mesenchymal transition stage. We also decipher circuits driving cranial and vagal neural crest formation and provide a broadly applicable high-throughput validation strategy for investigating single-cell transcriptomes in vertebrate GRNs in development, evolution, and disease.
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