Dysregulated endocardial TGFβ signaling and mesenchymal transformation result in heart outflow tract septation failure.
Dysregulated endocardial TGFβ signaling and mesenchymal transformation result in heart outflow tract septation failure.
复制标题
心内膜 TGFβ 信号传导失调和间充质转化导致心脏流出道分隔失败。
DOI：
10.1016/j.ydbio.2015.09.021
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发表时间：
2016
影响因子：
2.7
通讯作者：
Sucov,HenryM
中科院分区：
文献类型：
--
作者：
Ma,Mancheong;Li,Peng;Shen,Hua;Estrada,KristineD;Xu,Jian;Kumar,SRam;Sucov,HenryM
Heart outflow tract septation in mouse embryos carrying mutations in retinoic acid receptor genes fails with complete penetrance. In this mutant background, ectopic TGFβ signaling in the distal outflow tract is responsible for septation failure, but it was uncertain what tissue was responsive to ectopic TGFβ and why this response interfered with septation. By combining RAR gene mutation with tissue-specific Cre drivers and a conditional type II TGFβ receptor (Tgfbr2) allele, we determined that ectopic activation of TGFβ signaling in the endocardium is responsible for septation defects. Ectopic TGFβ signaling results in ectopic mesenchymal transformation of the endocardium and thereby in improperly constituted distal OFT cushions. Our analysis highlights the interactions between myocardium, endocardium, and neural crest cells in outflow tract morphogenesis, and demonstrates the requirement for proper TGFβ signaling in outflow tract cushion organization and septation.
