title: Colonic epithelial expression of ErbB2 is required for postnatal maintenance of the enteric nervous system.
abstract: We utilized the Cre-LoxP system to establish erbB2 conditional mutant mice in order to investigate the role of erbB2 in postnatal development of the enteric nervous system. The erbB2/nestin-Cre conditional mutants exhibit retarded growth, distended colons, and premature death, resembling human Hirschsprung's disease. Enteric neurons and glia are present at birth in the colon of erbB2/nestin-Cre mutants; however, a marked loss of multiple classes of enteric neurons and glia occurs by 3 weeks of age. Furthermore, we demonstrate that the requirement for erbB2 in maintaining the enteric nervous system is not cell autonomous, but rather erbB2 signaling in the colonic epithelia is required for the postnatal survival of enteric neurons and glia.
authors.affiliation: The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Crone
authors.forename: Alejandra
authors.initials: A
authors.lastname: Negro
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
authors.forename: Marco
authors.initials: M
authors.lastname: Giovannini
authors.forename: Kuo-Fen
authors.initials: KF
authors.lastname: Lee
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics*; D002678:Chimera; D003106:Colon / Q000166:cytology / Q000254:growth & development* / Q000294:innervation*; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006627:Hirschsprung Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D019426:Integrases / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins; D064231:Nestin; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
chemical_list: D019426:Integrases; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D018719:Erb-b2 Receptor Tyrosine Kinases; D014764:Viral Proteins; C577484:NES protein, human; C577485:Nes protein, mouse; C045073:Cre recombinase