Collagen 18 and agrin are secreted by neural crest cells to remodel their microenvironment and regulate their migration during enteric nervous system development

Nandor Nagy, Csilla Barad, Ryo Hotta, Sukhada Bhave, Emily Arciero, David Dora, Allan M. Goldstein

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The enteric nervous system (ENS) arises from neural crest cells that migrate, proliferate, and differentiate into enteric neurons and glia within the intestinal wall. Many extracellular matrix (ECM) components are present in the embryonic gut, but their role in regulating ENS development is largely unknown. Here, we identify heparan sulfate proteoglycan proteins, including collagen XVIII (Col18) and agrin, as important regulators of enteric neural crest-derived cell (ENCDC) development. In developing avian hindgut, Col18 is expressed at the ENCDC wavefront, while agrin expression occurs later. Both proteins are normally present around enteric ganglia, but are absent in aganglionic gut. Using chick-mouse intestinal chimeras and enteric neurospheres, we show that vagal- and sacral-derived ENCDCs from both species secrete Col18 and agrin. Whereas glia express Col18 and agrin, enteric neurons only express the latter. Functional studies demonstrate that Col18 is permissive whereas agrin is strongly inhibitory to ENCDC migration, consistent with the timing of their expression during ENS development. We conclude that ENCDCs govern their own migration by actively remodeling their microenvironment through secretion of ECM proteins.

Original languageEnglish
Article numberdev160317
JournalDevelopment (Cambridge)
Volume145
Issue number9
DOIs
Publication statusPublished - May 2018

Keywords

  • Agrin
  • Chicken
  • Collagen 18
  • Enteric nervous system
  • Extracellular matrix
  • Hirschsprung disease
  • Mouse
  • Neural crest cells

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Collagen 18 and agrin are secreted by neural crest cells to remodel their microenvironment and regulate their migration during enteric nervous system development'. Together they form a unique fingerprint.

  • Cite this