Lineage-dependent spatial and functional organization of the mammalian enteric nervous system

Reena Lasrado, Werend Boesmans, Jens Kleinjung, Carmen Pin, Donald Bell, Leena Bhaw, Sarah McCallum, Hui Zong, Liqun Luo, Hans Clevers, Pieter Vanden Berghe, Vassilis Pachnis

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)722-726
Number of pages5
JournalScience
Volume356
Issue number6339
DOIs
Publication statusPublished - 19 May 2017

Keywords

  • Journal Article
  • Research Support, Non-U.S. Gov't

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