tal1 Regulates the formation of intercellular junctions and the maintenance of identity in the endocardium.
tal1 Regulates the formation of intercellular junctions and the maintenance of identity in the endocardium.
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tal1 调节细胞间连接的形成和心内膜特性的维持。
DOI：
10.1016/j.ydbio.2013.09.019
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发表时间：
2013
影响因子：
2.7
通讯作者：
Yelon,Deborah
中科院分区：
文献类型：
--
作者：
Schumacher,JenniferA;Bloomekatz,Joshua;Garavito-Aguilar,ZayraV;Yelon,Deborah
心内膜形成心管的内衬，它使血液流动，并在瓣膜和小梁形成期间与心肌相互作用。虽然许多研究已经确定了心肌形态发生的调节因子，但对控制心肌内膜形态发生的分子知之甚少。先前的研究表明bHLH转录因子Tal 1参与了内膜管的形成：在缺乏Tal 1的斑马鱼胚胎中，内膜细胞在心室内形成了一个混乱的团块，并且不填充心房。通过卵裂球移植，我们发现Tal 1在调节内皮细胞延伸中起细胞自主作用，表明Tal 1活性影响单个内皮细胞的行为。内分泌行为缺陷起源于内分泌形态发生的最早阶段：内分泌细胞不能在中线处形成有粘性的单层，而是紧密地聚集在一起形成多层聚集体。此外，紧密连接蛋白ZO-1在thetal 1缺陷的内皮细胞中定位错误，表明细胞间连接形成缺陷。此外，我们发现thetal 1缺陷的内皮细胞不能保持其身份，随着时间的推移，越来越多的thetal 1缺陷的内皮细胞启动心肌基因表达。然而，在thetal 1缺陷型内皮细胞中，细胞间连接形成缺陷的发生早于异位心肌基因表达的发生。因此，我们提出了一个模型，其中Tal 1在调节内皮细胞间连接的形成和维持内皮细胞的身份有不同的作用。
The endocardium forms the inner lining of the heart tube, where it enables blood flow and also interacts with the myocardium during the formation of valves and trabeculae. Although a number of studies have identified regulators in the morphogenesis of the myocardium, relatively little is known about the molecules that control endocardial morphogenesis. Prior work has implicated the bHLH transcription factor Tal1 in endocardial tube formation: in zebrafish embryos lacking Tal1, endocardial cells form a disorganized mass within the ventricle and do not populate the atrium. Through blastomere transplantation, we find thattal1plays a cell-autonomous role in regulating endocardial extension, suggesting that Tal1 activity influences the behavior of individual endocardial cells. The defects in endocardial behavior intal1-deficient embryos originate during the earliest steps of endocardial morphogenesis:tal1-deficient endocardial cells fail to generate a cohesive monolayer at the midline and instead pack tightly together into a multi-layered aggregate. Moreover, the tight junction protein ZO-1 is mislocalized in thetal1-deficient endocardium, indicating a defect in intercellular junction formation. In addition, we find that thetal1-deficient endocardium fails to maintain its identity; over time, a progressively increasing number oftal1-deficient endocardial cells initiate myocardial gene expression. However, the onset of defects in intercellular junction formation precedes the onset of ectopic myocardial gene expression in thetal1-deficient endocardium. We therefore propose a model in which Tal1 has distinct roles in regulating the formation of endocardial intercellular junctions and maintaining endocardial identity.