BMP signaling is necessary for neural crest cell migration and ganglion formation in the enteric nervous system

Allan M. Goldstein, Katherine C. Brewer, Adele M. Doyle, N. Nagy, Drucilla J. Roberts

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

The enteric nervous system (ENS) is derived from neural crest cells that migrate along the gastrointestinal tract to form a network of neurons and glia that are essential for regulating intestinal motility. Despite the number of genes known to play essential roles in ENS development, the molecular etiology of congenital disorders affecting this process remains largely unknown. To determine the role of bone morphogenetic protein (BMP) signaling in ENS development, we first examined the expression of bmp2, bmp4, and bmprII during hindgut development and find these strongly expressed in the ENS. Moreover, functional BMP signaling, demonstrated by the expression of phosphorylated Smad1/5/8, is present in the enteric ganglia. Inhibition of BMP activity by noggin misexpression within the developing gut, both in ovo and in vitro, inhibits normal migration of enteric neural crest cells. BMP inhibition also leads to hypoganglionosis and failure of enteric ganglion formation, with crest cells unable to cluster into aggregates. Abnormalities of migration and ganglion formation are the hallmarks of two human intestinal disorders, Hirschsprung's disease and intestinal neuronal dysplasia. Our results support an essential role for BMP signaling in these aspects of ENS development and provide a basis for further investigation of these proteins in the etiology of neuro-intestinal disorders.

Original languageEnglish
Pages (from-to)821-833
Number of pages13
JournalMechanisms of Development
Volume122
Issue number6
DOIs
Publication statusPublished - Jun 2005

Fingerprint

Enteric Nervous System
Bone Morphogenetic Proteins
Neural Crest
Ganglia
Cell Movement
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Hirschsprung Disease
Gastrointestinal Motility
Neuroglia
Gastrointestinal Tract
Neurons
Genes
Proteins

Keywords

  • BMP
  • Chick
  • Enteric nervous system
  • Gut development
  • Hirschsprung's disease
  • Noggin

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

Cite this

BMP signaling is necessary for neural crest cell migration and ganglion formation in the enteric nervous system. / Goldstein, Allan M.; Brewer, Katherine C.; Doyle, Adele M.; Nagy, N.; Roberts, Drucilla J.

In: Mechanisms of Development, Vol. 122, No. 6, 06.2005, p. 821-833.

Research output: Contribution to journalArticle

Goldstein, Allan M. ; Brewer, Katherine C. ; Doyle, Adele M. ; Nagy, N. ; Roberts, Drucilla J. / BMP signaling is necessary for neural crest cell migration and ganglion formation in the enteric nervous system. In: Mechanisms of Development. 2005 ; Vol. 122, No. 6. pp. 821-833.
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