Lineage-dependent spatial and functional organization of the mammalian enteric nervous system
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Reena Lasrado Werend Boesmans Jens Kleinjung Carmen Pin Donald Bell Leena Bhaw Sarah Mccallum Hui Zong Liqun Luo Hans Clevers Pieter Vanden Berghe Vassilis PachnisAbstract
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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Journal Science
Volume 356
Issue number 6339
Pages 722-726
Available online
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Publisher website (DOI) 10.1126/science.aam7511
Europe PubMed Central 28522527
Pubmed 28522527
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