Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages.

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 Biol

journal_title

Nature cell biology

authors

Ling ITC,Sauka-Spengler T

doi

10.1038/s41556-019-0428-9

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

1504-1517

issue

12

eissn

1465-7392

issn

1476-4679

pii

10.1038/s41556-019-0428-9

journal_volume

21

pub_type

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