Focal adhesions are essential to drive zebrafish heart valve morphogenesis
Focal adhesions are essential to drive zebrafish heart valve morphogenesis
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DOI：
10.1083/jcb.201807175
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发表时间：
2019-03-01
影响因子：
7.8
通讯作者：
Stainier, Didier Y. R.
中科院分区：
文献类型：
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作者：
Gunawan, Felix;Gentile, Alessandra;Stainier, Didier Y. R.
阐明塑造脊椎动物心脏瓣膜的形态发生事件以及防止逆行血流的复杂结构对于了解瓣膜发育和畸变至关重要。在这里，我们使用斑马鱼房室（AV）瓣膜在真实的时间和单细胞分辨率下研究这些事件。我们报告了AV内皮细胞（EC）集体迁移到细胞外基质（ECM）的初始事件，以及随后的重排形成小叶。我们在功能上表征了瓣膜形态发生过程中基于整合素的粘着斑（FA），细胞-ECM相互作用的关键介质。使用转基因阻断FA信号，特别是在AV EC以及功能丧失的方法，我们表明，FA信号介导的整合素α 5 β 1和塔林1促进AV EC迁移和整体成形的瓣膜小叶。总之，我们的研究揭示了在体内驱动心脏瓣膜形态发生的关键过程，并建立了斑马鱼AV瓣膜作为脊椎动物模型来研究FA调节的组织形态发生。
Elucidating the morphogenetic events that shape vertebrate heart valves, complex structures that prevent retrograde blood flow, is critical to understanding valvular development and aberrations. Here, we used the zebrafish atrioventricular (AV) valve to investigate these events in real time and at single-cell resolution. We report the initial events of collective migration of AV endocardial cells (ECs) into the extracellular matrix (ECM), and their subsequent rearrangements to form the leaflets. We functionally characterize integrin-based focal adhesions (FAs), critical mediators of cell-ECM interactions, during valve morphogenesis. Using transgenes to block FA signaling specifically in AV ECs as well as loss-of-function approaches, we show that FA signaling mediated by Integrin alpha 5 beta 1 and Talin1 promotes AV EC migration and overall shaping of the valve leaflets. Altogether, our investigation reveals the critical processes driving cardiac valve morphogenesis in vivo and establishes the zebrafish AV valve as a vertebrate model to study FA-regulated tissue morphogenesis.