High-resolution imaging of cardiomyocyte behavior reveals two distinct steps in ventricular trabeculation
High-resolution imaging of cardiomyocyte behavior reveals two distinct steps in ventricular trabeculation
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DOI：
10.1242/dev.098632
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发表时间：
2014-02-01
期刊：
影响因子：
4.6
通讯作者：
Stainier, Didier Y. R.
中科院分区：
文献类型：
--
作者：
Staudt, David W.;Liu, Jiandong;Stainier, Didier Y. R.
在发育过程中，脊椎动物心脏经历了一系列复杂的形态发生过程，将其从简单的心肌上皮细胞转变为其功能所需的复杂3D结构。这些过程之一导致小梁的形成，以优化心室的内部结构，以实现有效的传导和收缩。尽管骨小梁在心脏的发育和生理中起着重要作用，但对其形成机制知之甚少。利用3D延时成像的跳动斑马鱼心脏，我们观察到心脏小梁形成的启动可以分为两个过程。在任何心肌细胞体进入小梁层之前，心肌细胞延伸突起，沿着相邻的细胞-细胞连接侵入腔。这些突起可以在小梁层内相互作用以形成新的细胞-细胞接触。随后，心肌细胞收缩它们的近腔表面，将它们的细胞体移动到小梁层中，同时制造更多的突起。我们还研究了小梁形成缺陷动物中这些突起的形成，包括erbb 2突变体，缺乏心脏收缩和血流的tnnt 2a morphants，以及缺乏心房收缩和血流减少的myh 6 morphants。我们发现，与野生型心肌细胞相比，erbb 2突变体中的心肌细胞不太可能形成突起，tnnt 2a变形体中的心肌细胞形成的突起不太稳定，myh 6变形体中的心肌细胞每个细胞延伸的突起更少。因此，通过跳动心脏的详细4D成像，我们已经确定了心脏小梁形成的新细胞行为。
Over the course of development, the vertebrate heart undergoes a series of complex morphogenetic processes that transforms it from a simple myocardial epithelium to the complex 3D structure required for its function. One of these processes leads to the formation of trabeculae to optimize the internal structure of the ventricle for efficient conduction and contraction. Despite the important role of trabeculae in the development and physiology of the heart, little is known about their mechanism of formation. Using 3D time-lapse imaging of beating zebrafish hearts, we observed that the initiation of cardiac trabeculation can be divided into two processes. Before any myocardial cell bodies have entered the trabecular layer, cardiomyocytes extend protrusions that invade luminally along neighboring cell-cell junctions. These protrusions can interact within the trabecular layer to form new cell-cell contacts. Subsequently, cardiomyocytes constrict their abluminal surface, moving their cell bodies into the trabecular layer while elaborating more protrusions. We also examined the formation of these protrusions in trabeculation-deficient animals, including erbb2 mutants, tnnt2a morphants, which lack cardiac contractions and flow, and myh6 morphants, which lack atrial contraction and exhibit reduced flow. We found that, compared with cardiomyocytes in wild-type hearts, those in erbb2 mutants were less likely to form protrusions, those in tnnt2a morphants formed less stable protrusions, and those in myh6 morphants extended fewer protrusions per cell. Thus, through detailed 4D imaging of beating hearts, we have identified novel cellular behaviors underlying cardiac trabeculation.