Cardiovascular malformations with normal smooth muscle differentiation in neural crest-specific type II TGF[beta] receptor (Tgfbr2) mutant mice

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2005.11.008 Byline: Bibha Choudhary (a), Yoshihiro Ito (b), Takako Makita (a), Tomoyo Sasaki (b), Yang Chai (b), Henry M. Sucov (a) Keywords: Neural crest; TGF[beta]; Type II receptor; Persistent truncus arteriosus; Interrupted aortic arch; DiGeorge syndrome Abstract: Previous studies have demonstrated that TGF[beta] induces a smooth muscle fate in primary neural crest cells in culture. By crossing a conditional allele of the type II TGF[beta] receptor with the neural crest-specific Wnt1cre transgene, we have addressed the in vivo requirement for TGF[beta] signaling in smooth muscle specification and differentiation. We find that elimination of the TGF[beta] 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 TGF[beta] 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. Author Affiliation: (a) Institute for Genetic Medicine, Keck School of Medicine, School of Dentistry, University of Southern California, 2250 Alcazar St., IGM240, Los Angeles, CA 90033, USA (b) Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA Article History: Received 14 July 2005; Revised 26 October 2005; Accepted 8 November 2005