title: Cardiovascular malformations with normal smooth muscle differentiation in neural crest-specific type II TGFbeta receptor (Tgfbr2) mutant mice.
abstract: Previous studies have demonstrated that TGFbeta induces a smooth muscle fate in primary neural crest cells in culture. By crossing a conditional allele of the type II TGFbeta receptor with the neural crest-specific Wnt1cre transgene, we have addressed the in vivo requirement for TGFbeta signaling in smooth muscle specification and differentiation. We find that elimination of the TGFbeta receptor does not alter neural crest cell specification to a smooth muscle fate in the cranial or cardiac domains, and that a smooth muscle fate is not realized by trunk neural crest cells in either control or mutant embryos. Instead, mutant embryos exhibit with complete penetrance two very specific and mechanistically distinct cardiovascular malformations--persistent truncus arteriosus (PTA) and interrupted aortic arch (IAA-B). Pharyngeal organ defects such as those seen in models of DiGeorge syndrome were not observed, arguing against an early perturbation of the cardiac neural crest cell lineage. We infer that TGFbeta is an essential morphogenic signal for the neural crest cell lineage in specific aspects of cardiovascular development, although one that is not required for smooth muscle differentiation.
authors.affiliation: Institute for Genetic Medicine, Keck School of Medicine, School of Dentistry, University of Southern California, 2250 Alcazar St., IGM240, Los Angeles, 90033, USA.
authors.forename: Bibha
authors.initials: B
authors.lastname: Choudhary
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ito
authors.forename: Takako
authors.initials: T
authors.lastname: Makita
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Sasaki
authors.forename: Yang
authors.initials: Y
authors.lastname: Chai
authors.forename: Henry M
authors.initials: HM
authors.lastname: Sucov
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D001934:Branchial Region / Q000196:embryology / Q000378:metabolism; D002319:Cardiovascular System / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D009154:Mutation; D009432:Neural Crest / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011651:Pulmonary Artery / Q000166:cytology / Q000196:embryology / Q000502:physiology; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D019076:Transgenes; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D051153:Wnt Proteins; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; C045073:Cre recombinase; D019426:Integrases