Choudhary Bibha, Ito Yoshihiro, Makita Takako, Sasaki Tomoyo, Chai Yang, Sucov Henry M
Institute for Genetic Medicine, Keck School of Medicine, School of Dentistry, University of Southern California, 2250 Alcazar St., IGM240, Los Angeles, 90033, USA.
Dev Biol. 2006 Jan 15;289(2):420-9. doi: 10.1016/j.ydbio.2005.11.008. Epub 2005 Dec 5.
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.
先前的研究表明，转化生长因子β（TGFβ）可在培养的原代神经嵴细胞中诱导平滑肌命运。通过将II型TGFβ受体的条件等位基因与神经嵴特异性Wnt1cre转基因杂交，我们探讨了TGFβ信号在平滑肌特化和分化中的体内需求。我们发现，消除TGFβ受体不会改变神经嵴细胞在颅部或心脏区域向平滑肌命运的特化，并且在对照或突变胚胎中，躯干神经嵴细胞都不会实现平滑肌命运。相反，突变胚胎完全显性地表现出两种非常特殊且机制不同的心血管畸形——永存动脉干（PTA）和主动脉弓中断（IAA-B）。未观察到如DiGeorge综合征模型中所见的咽器官缺陷，这表明心脏神经嵴细胞谱系未受到早期干扰。我们推断，TGFβ在心血管发育的特定方面是神经嵴细胞谱系必不可少的形态发生信号，尽管它不是平滑肌分化所必需的。
