Dual embryonic origin of the mammalian enteric nervous system

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage / genetics
  • Duodenum / embryology
  • Duodenum / innervation
  • Duodenum / metabolism
  • Endoderm / cytology
  • Endoderm / embryology
  • Endoderm / metabolism
  • Enteric Nervous System / cytology
  • Enteric Nervous System / embryology*
  • Enteric Nervous System / metabolism
  • Gene Expression Regulation, Developmental
  • HMGB Proteins / genetics
  • HMGB Proteins / metabolism
  • Hepatocyte Nuclear Factor 3-beta / genetics
  • Hepatocyte Nuclear Factor 3-beta / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Neural Crest / cytology
  • Neural Crest / embryology
  • Neural Crest / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Pancreas / embryology
  • Pancreas / innervation
  • Pancreas / metabolism
  • SOXF Transcription Factors / genetics
  • SOXF Transcription Factors / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism

Substances

  • Foxa2 protein, mouse
  • HMGB Proteins
  • Homeodomain Proteins
  • SOXF Transcription Factors
  • Sox17 protein, mouse
  • Trans-Activators
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • pancreatic and duodenal homeobox 1 protein
  • Hepatocyte Nuclear Factor 3-beta