Temporal and distinct TGFβ ligand requirements during mouse and avian endocardial cushion morphogenesis
Temporal and distinct TGFβ ligand requirements during mouse and avian endocardial cushion morphogenesis
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DOI：
10.1006/dbio.2002.0731
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发表时间：
2002-08-01
影响因子：
2.7
通讯作者：
Klewer, SE
中科院分区：
文献类型：
--
作者：
Camenisch, TD;Molin, DGM;Klewer, SE
发育不全心脏房室管内膜垫的形成需要上皮细胞向间充质细胞转化。这是一个由多种细胞外信号和转导途径调控的复杂发育过程。胶原蛋白凝胶试验，长期用于检查内皮细胞垫的发展，在鸟类模型，现在被用来研究基因工程小鼠模型异常心脏形态发生。在这项研究中，我们确定了鸟类和小鼠培养的内膜垫外植体的种间差异。考虑到这些观察到的形态学差异，我们还定义了小鼠内膜垫形态发生过程中TGF β 2和TGF β 3的时间要求。TGF β 2和TGF β 3阻断抗体分别抑制禽类外植体中的内皮细胞活化和转化。相反，中和TGF β 2抑制小鼠中的细胞转化，而TGF β 3抗体对活化或转化事件没有影响。这种对TGF β 2的功能性需求伴随着TGF β 2的表达，而不是TGF β 3，在小鼠内皮细胞垫内与转化同时发生。因此，TGF β 2和TGF β 3似乎是鸡EMT的完整形态发生程序所必需的，但只有TGF β 2表达，并且是哺乳动物内膜垫细胞转化的必需品。(C)2002 Elsevier Science（美国）。
The formation of endocardial cushions in the atrioventricular (AV) canal of the rudimentary heart requires epithelial-to-mesenchymal cell transformation (EMT). This is a complex developmental process regulated by multiple extracellular signals and transduction pathways. A collagen gel assay, long used to examine endocardial cushion development in avian models, is now being employed to investigate genetically engineered mouse models with abnormal heart morphogenesis. In this study, we determine interspecies variations for avian and mouse cultured endocardial cushion explants. Considering these observed morphologic differences, we also define the temporal requirements for TGFbeta2 and TGFbeta3 during mouse endocardial cushion morphogenesis. TGFbeta2 and TGFbeta3 blocking antibodies inhibit endothelial cell activation and transformation, respectively, in avian explants. In contrast, neutralizing TGFbeta2 inhibits cell transformation in the mouse, while TGFbeta3 antibodies have no effect on activation or transformation events. This functional requirement for TGFbeta2 is concomitant with expression of TGFbeta2, but not TGFbeta3, within mouse endocardial cushions at a time coincident with transformation. Thus, both TGFbeta2 and TGFbeta3 appear necessary for the full morphogenetic program of EMT in the chick, but only TGFbeta2 is expressed and obligatory for mammalian endocardial cushion cell transformation. (C) 2002 Elsevier Science (USA).