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

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 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. (c) 2005 Elsevier Inc. All rights reserved.