Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages
Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages
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DOI：
10.1038/s41556-019-0428-9
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发表时间：
2019-12-01
影响因子：
21.3
通讯作者：
Sauka-Spengler, Tatjana
中科院分区：
文献类型：
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作者：
Ling, Irving T. C.;Sauka-Spengler, Tatjana
肠神经系统（ENS）主要来源于迷走神经嵴（VNC）细胞，这些细胞来自后脑尾部，侵入前肠并填充胃肠道。然而，基因调控网络（GRN）编排VNC的早期规范仍然未知。使用EdnrB增强子，我们在鸟类模型中生成了VNC的染色质和转录景观的综合时间图，揭示了三个VNC细胞簇（神经，神经源性和间质），每个细胞簇在神经管分层之前都预先确定了表观遗传。我们鉴定并功能验证了介导每个程序的调控核心（Sox10/Tfap2B/SoxB/Hbox），并阐明了它们与其他时空特异性转录因子（bHLH/NR）的组合活性。我们对体内VNC-GRN的整体解构揭示了可能影响肠内神经病变中不同神经表型的关键早期调节机制。
The enteric nervous system (ENS) predominantly originates from vagal neural crest (VNC) cells that emerge from the caudal hindbrain, invade the foregut and populate the gastrointestinal tract. However, the gene regulatory network (GRN) orchestrating the early specification of VNC remains unknown. Using an EdnrB enhancer, we generated a comprehensive temporal map of the chromatin and transcriptional landscape of VNC in the avian model, revealing three VNC cell clusters (neural, neurogenic and mesenchymal), each predetermined epigenetically prior to neural tube delamination. We identify and functionally validate regulatory cores (Sox10/Tfap2B/SoxB/Hbox) mediating each programme and elucidate their combinatorial activities with other spatiotemporally specific transcription factors (bHLH/NR). Our global deconstruction of the VNC-GRN in vivo sheds light on critical early regulatory mechanisms that may influence the divergent neural phenotypes in enteric neuropathies.