Scherz Paul J, Huisken Jan, Sahai-Hernandez Pankaj, Stainier Didier Y R
Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Development. 2008 Mar;135(6):1179-87. doi: 10.1242/dev.010694. Epub 2008 Feb 13.
Knowing how mutations disrupt the interplay between atrioventricular valve (AVV) morphogenesis and function is crucial for understanding how congenital valve defects arise. Here, we use high-speed fluorescence microscopy to investigate AVV morphogenesis in zebrafish at cellular resolution. We find that valve leaflets form directly through a process of invagination, rather than first forming endocardial cushions. There are three phases of valve function in embryonic development. First, the atrioventricular canal (AVC) is closed by the mechanical action of the myocardium, rolls together and then relaxes. The growing valve leaflets serve to block the canal during the roll and, depending on the developmental stage, either expand or hang down as a leaflet to block the canal. These steps are disrupted by the subtle morphological changes that result from inhibiting ErbB-, TGFbeta-or Cox2 (Ptgs2)-dependent signaling. Cox2 inhibition affects valve development due to its effect on myocardial cell size and shape, which changes the morphology of the ventricle and alters valve geometry. Thus, different signaling pathways regulate distinct aspects of the behavior of individual cells during valve morphogenesis, thereby influencing specific facets of valve function.
了解突变如何破坏房室瓣（AVV）形态发生与功能之间的相互作用，对于理解先天性瓣膜缺陷的产生机制至关重要。在此，我们使用高速荧光显微镜在细胞分辨率水平上研究斑马鱼的房室瓣形态发生。我们发现瓣膜小叶直接通过内陷过程形成，而不是先形成心内膜垫。胚胎发育过程中有三个瓣膜功能阶段。首先，房室管（AVC）通过心肌的机械作用关闭，卷合在一起然后松弛。生长中的瓣膜小叶在卷合过程中起到阻塞管道的作用，并且根据发育阶段，要么扩张要么作为小叶垂下以阻塞管道。这些步骤会因抑制ErbB、TGFβ或Cox2（Ptgs2）依赖性信号传导所导致的细微形态变化而受到干扰。Cox2抑制会影响瓣膜发育，因为它对心肌细胞大小和形状有影响，从而改变心室形态并改变瓣膜几何形状。因此，不同的信号通路在瓣膜形态发生过程中调节单个细胞行为的不同方面，进而影响瓣膜功能的特定方面。
