PMID:15337776

Citation	Fu, M, Lui, VC, Sham, MH, Pachnis, V and Tam, PK (2004) Sonic hedgehog regulates the proliferation, differentiation, and migration of enteric neural crest cells in gut. J. Cell Biol. 166:673-84
Abstract	Enteric neural crest cells (NCCs) migrate and colonize the entire gut and proliferate and differentiate into neurons and glia of the enteric nervous system in vertebrate embryos. We have investigated the mitogenic and morphogenic functions of Sonic hedgehog (Shh) on enteric NCCs in cell and organ culture. Enteric NCCs expressed Shh receptor Patched and transcripts encoding the Shh signal transducer (Gli1). Shh promoted the proliferation and inhibited the differentiation of NCCs. The pro-neurogenic effect of glial cell line--derived neurotrophic factor (GDNF) on NCCs was abolished by Shh. In gut explants, NCCs migrated from the explants onto the adjacent substratum if GDNF was added, whereas addition of Shh abolished this migration. Neuronal differentiation and coalescence of neural crest--derived cells into myenteric plexuses in explants was repressed by the addition of Shh. Our data suggest that Shh controls the proliferation and differentiation of NCCs and modulates the responsiveness of NCCs toward GDNF inductions.
Links	PubMed PMC2172437 Online version:10.1083/jcb.200401077
Keywords	Animals; Biological Markers; Cell Differentiation/drug effects; Cell Differentiation/genetics; Cell Division/drug effects; Cell Division/genetics; Cell Movement/drug effects; Cell Movement/genetics; Cells, Cultured; Enteric Nervous System/cytology; Enteric Nervous System/embryology; Enteric Nervous System/metabolism; Gastrointestinal Tract/cytology; Gastrointestinal Tract/embryology; Gastrointestinal Tract/innervation; Glial Cell Line-Derived Neurotrophic Factor; Hedgehog Proteins; Intracellular Signaling Peptides and Proteins; Kruppel-Like Transcription Factors; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mice; Mice, Inbred ICR; Mice, Transgenic; Myenteric Plexus/cytology; Myenteric Plexus/embryology; Myenteric Plexus/metabolism; Nerve Growth Factors/antagonists & inhibitors; Nerve Growth Factors/metabolism; Nerve Tissue Proteins/metabolism; Neural Crest/cytology; Neural Crest/embryology; Neural Crest/metabolism; Neurons/cytology; Neurons/drug effects; Neurons/metabolism; Organ Culture Techniques; Receptors, Cell Surface; Spheroids, Cellular/cytology; Spheroids, Cellular/drug effects; Spheroids, Cellular/metabolism; Stem Cells/cytology; Stem Cells/drug effects; Stem Cells/metabolism; Trans-Activators/genetics; Trans-Activators/metabolism; Trans-Activators/pharmacology; Transcription Factors/genetics; Transcription Factors/metabolism
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