Institut de Biologie de l'École Normale Supérieure (IBENS), École Normale Supérieure, CNRS, INSERM, PSL Research University, 75005 Paris, France.
Stem Cells and Regenerative Medicine, Birth Defects Research Centre, University College London Great Ormond Street Institute of Child Health, WC1N 1EH London, United Kingdom.
Proc Natl Acad Sci U S A. 2017 Nov 7;114(45):11980-11985. doi: 10.1073/pnas.1710308114. Epub 2017 Oct 24.
Most of the enteric nervous system derives from the "vagal" neural crest, lying at the level of somites 1-7, which invades the digestive tract rostro-caudally from the foregut to the hindgut. Little is known about the initial phase of this colonization, which brings enteric precursors into the foregut. Here we show that the "vagal crest" subsumes two populations of enteric precursors with contrasted origins, initial modes of migration, and destinations. Crest cells adjacent to somites 1 and 2 produce Schwann cell precursors that colonize the vagus nerve, which in turn guides them into the esophagus and stomach. Crest cells adjacent to somites 3-7 belong to the crest streams contributing to sympathetic chains: they migrate ventrally, seed the sympathetic chains, and colonize the entire digestive tract thence. Accordingly, enteric ganglia, like sympathetic ones, are atrophic when deprived of signaling through the tyrosine kinase receptor ErbB3, while half of the esophageal ganglia require, like parasympathetic ones, the nerve-associated form of the ErbB3 ligand, Neuregulin-1. These dependencies might bear relevance to Hirschsprung disease, with which alleles of are associated.
大部分肠神经系统源于“迷走”神经嵴，位于体节 1-7 水平，从前肠到后肠，从头侧向尾侧侵入消化道。关于这种殖民的初始阶段，即肠前体细胞进入前肠，我们知之甚少。在这里，我们表明“迷走神经嵴”包含两种具有不同起源、初始迁移模式和目的地的肠前体细胞群。紧邻体节 1 和 2 的嵴细胞产生施万细胞前体细胞，这些细胞定植于迷走神经，迷走神经反过来引导它们进入食管和胃。紧邻体节 3-7 的嵴细胞属于交感神经链的嵴流：它们向腹侧迁移，定植于交感神经链，并由此定植于整个消化道。因此，肠神经节与交感神经节一样，当通过酪氨酸激酶受体 ErbB3 信号缺失时会发生萎缩，而一半的食管神经节与副交感神经节一样，需要神经相关形式的 ErbB3 配体 Neuregulin-1。这些依赖性可能与先天性巨结肠病有关，与该疾病相关的等位基因是。
