Abstract:
: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.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Ling ITC,Sauka-Spengler Tdoi
10.1038/s41556-019-0428-9subject
Has Abstractpub_date
2019-12-01 00:00:00pages
1504-1517issue
12eissn
1465-7392issn
1476-4679pii
10.1038/s41556-019-0428-9journal_volume
21pub_type
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