Neurodevelopment: 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

doi:10.1126/science.aam7511

Neurodevelopment: 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-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 RETas 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 language	English
Pages (from-to)	722-726
Number of pages	5
Journal	Science
Volume	356
Issue number	6339
DOIs	https://doi.org/10.1126/science.aam7511
Publication status	Published - 19 May 2017

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title = "Neurodevelopment: Lineage-dependent spatial and functional organization of the mammalian enteric nervous system",

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 RETas 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.",

author = "Reena Lasrado and Werend Boesmans and Jens Kleinjung and Carmen Pin and Donald Bell and Leena Bhaw and Sarah McCallum and Hui Zong and Liqun Luo and Hans Clevers and \{Vanden Berghe\}, Pieter and Vassilis Pachnis",

note = "Funding Information: P.V.B. was supported by Fonds voor Wetenschappelijk Onderzoek (FWO-Flanders; grants G.0510.10 and G.0921.015). W.B. was a recipient of a postdoctoral fellowship from FWO-Flanders. C.P. acknowledges the support of the UK Biotechnology and Biological Sciences Research Council (BBSRC) Gut Health and Food Safety Programme Grant (BB/J004529/1). Work in V.P.'s laboratory is supported by the BBSRC (BB/L022974/1), the UK Medical Research Council (MRC), and the Francis Crick Institute (which receives funding from the MRC, Cancer Research UK, and the Wellcome Trust). Publisher Copyright: {\textcopyright} 2016 by the American Association for the Advancement of Science; all rights reserved.",

year = "2017",

month = may,

day = "19",

doi = "10.1126/science.aam7511",

language = "English",

volume = "356",

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T2 - Lineage-dependent spatial and functional organization of the mammalian enteric nervous system

AU - Lasrado, Reena

AU - Boesmans, Werend

AU - Kleinjung, Jens

AU - Pin, Carmen

AU - Bell, Donald

AU - Bhaw, Leena

AU - McCallum, Sarah

AU - Zong, Hui

AU - Luo, Liqun

AU - Clevers, Hans

AU - Vanden Berghe, Pieter

AU - Pachnis, Vassilis

N1 - Funding Information: P.V.B. was supported by Fonds voor Wetenschappelijk Onderzoek (FWO-Flanders; grants G.0510.10 and G.0921.015). W.B. was a recipient of a postdoctoral fellowship from FWO-Flanders. C.P. acknowledges the support of the UK Biotechnology and Biological Sciences Research Council (BBSRC) Gut Health and Food Safety Programme Grant (BB/J004529/1). Work in V.P.'s laboratory is supported by the BBSRC (BB/L022974/1), the UK Medical Research Council (MRC), and the Francis Crick Institute (which receives funding from the MRC, Cancer Research UK, and the Wellcome Trust). Publisher Copyright: © 2016 by the American Association for the Advancement of Science; all rights reserved.

PY - 2017/5/19

Y1 - 2017/5/19

N2 - 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 RETas 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.

AB - 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 RETas 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.

UR - https://www.scopus.com/pages/publications/85019852827

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DO - 10.1126/science.aam7511

M3 - Article

C2 - 28522527

AN - SCOPUS:85019852827

SN - 0036-8075

VL - 356

SP - 722

EP - 726

JO - Science

JF - Science

IS - 6339

ER -

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

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