Journal
SCIENCE
Volume 356, Issue 6339, Pages 722-726Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aam7511
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Funding
- Fonds voor Wetenschappelijk Onderzoek (FWO-Flanders) [G.0510.10, G.0921.015]
- FWO-Flanders
- UK Biotechnology and Biological Sciences Research Council (BBSRC) Gut Health and Food Safety Programme Grant [BB/J004529/1]
- BBSRC [BB/L022974/1]
- UK Medical Research Council (MRC)
- Francis Crick Institute from the MRC
- Cancer Research UK
- Wellcome Trust
- BBSRC [BB/L022974/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/L022974/1] Funding Source: researchfish
- The Francis Crick Institute [10128, 10002] Funding Source: researchfish
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The enteric nervous system (ENS) is essential for digestive function and gut homeostasis. Here we show that the amorphous neuroglia networks of the mouse ENS are composed of overlapping clonal units founded by postmigratory neural crest-derived progenitors. The spatial configuration of ENS clones depends on proliferation-driven local interactions of ENS progenitors with lineally unrelated neuroectodermal cells, the ordered colonization of the serosa-mucosa axis by clonal descendants, and gut expansion. Single-cell transcriptomics and mutagenesis analysis delineated dynamic molecular states of ENS progenitors and identified RET as a regulator of neurogenic commitment. Clonally related enteric neurons exhibit synchronous activity in response to network stimulation. Thus, lineage relationships underpin the organization of the peripheral nervous system.
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