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Dev Biol. 2019 Jan 15;445(2):256-270. doi: 10.1016/j.ydbio.2018.11.014. Epub 2018 Nov 22.

Dual embryonic origin of the mammalian enteric nervous system.

Author information

1
Department of Molecular Genetics, University of Toronto, Ontario M5S 1A8, Canada. Electronic address: ira.brokhman@gmail.com.
2
Department of Molecular Genetics, University of Toronto, Ontario M5S 1A8, Canada.
3
Helmholtz Zentrum München, Institute of Diabetes and Regeneration Research, 85764 Neuherberg, Germany.
4
Institute of Biomaterials and Biomedical Engineering", University of Toronto, Ontario M5S 3E1, Canada.
5
Department of Surgery, Division of Anatomy, University of Toronto, Ontario M5S 1A8, Canada.
6
Division of Pediatric Gastroenterology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
7
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305-5208, USA.
8
Department of Molecular Genetics, University of Toronto, Ontario M5S 1A8, Canada. Electronic address: derek.van.der.kooy@utoronto.ca.

Abstract

The enteric nervous system is thought to originate solely from the neural crest. Transgenic lineage tracing revealed a novel population of clonal pancreatic duodenal homeobox-1 (Pdx1)-Cre lineage progenitor cells in the tunica muscularis of the gut that produced pancreatic descendants as well as neurons upon differentiation in vitro. Additionally, an in vivo subpopulation of endoderm lineage enteric neurons, but not glial cells, was seen especially in the proximal gut. Analysis of early transgenic embryos revealed Pdx1-Cre progeny (as well as Sox-17-Cre and Foxa2-Cre progeny) migrating from the developing pancreas and duodenum at E11.5 and contributing to the enteric nervous system. These results show that the mammalian enteric nervous system arises from both the neural crest and the endoderm. Moreover, in adult mice there are separate Wnt1-Cre neural crest stem cells and Pdx1-Cre pancreatic progenitors within the muscle layer of the gut.

KEYWORDS:

Duodenum; Enteric nervous system; Lineage tracing; Neural crest; Pancreas; Pdx1-Cre-derived neural progenitors

PMID:
30472119
DOI:
10.1016/j.ydbio.2018.11.014
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