Cardiovascular malformations with normal smooth muscle differentiation in neural crest-specific type II TGFβ receptor (Tgfbr2) mutant mice
Cardiovascular malformations with normal smooth muscle differentiation in neural crest-specific type II TGFβ receptor (Tgfbr2) mutant mice
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DOI：
10.1016/j.ydbio.2005.11.008
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发表时间：
2006-01-15
影响因子：
2.7
通讯作者：
Sucov, HM
中科院分区：
文献类型：
--
作者：
Choudhary, B;Ito, Y;Sucov, HM
先前的研究表明，TGF beta 可诱导培养的原代神经嵴细胞的平滑肌命运。通过将 II 型 TGF β 受体的条件等位基因与神经嵴特异性 Wnt1cre 转基因杂交，我们解决了平滑肌规范和分化中 TGF β 信号传导的体内需求。我们发现消除 TGF 受体不会改变脑或心脏区域神经嵴细胞对平滑肌命运的规范，并且在对照或突变胚胎中躯干神经嵴细胞都没有实现平滑肌命运。相反，突变胚胎具有完全外显率，表现出两种非常特异且机制不同的心血管畸形——持续性动脉干（PTA）和主动脉弓中断（IAA-B）。没有观察到像迪乔治综合征模型中所见的咽器官缺陷，这反对心脏神经嵴细胞谱系的早期扰动。我们推断，TGFβ 是心血管发育特定方面神经嵴细胞谱系的重要形态发生信号，尽管平滑肌分化不是必需的。 (c) 2005 Elsevier Inc. 保留所有权利。
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.