Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
Development. 2010 Nov;137(22):3867-75. doi: 10.1242/dev.053736.
Cardiac trabeculation is a crucial morphogenetic process by which clusters of ventricular cardiomyocytes extrude and expand into the cardiac jelly to form sheet-like projections. Although it has been suggested that cardiac trabeculae enhance cardiac contractility and intra-ventricular conduction, their exact function in heart development has not been directly addressed. We found that in zebrafish erbb2 mutants, which we show completely lack cardiac trabeculae, cardiac function is significantly compromised, with mutant hearts exhibiting decreased fractional shortening and an immature conduction pattern. To begin to elucidate the cellular mechanisms of ErbB2 function in cardiac trabeculation, we analyzed erbb2 mutant hearts more closely and found that loss of ErbB2 activity resulted in a complete absence of cardiomyocyte proliferation during trabeculation stages. In addition, based on data obtained from proliferation, lineage tracing and transplantation studies, we propose that cardiac trabeculation is initiated by directional cardiomyocyte migration rather than oriented cell division, and that ErbB2 cell-autonomously regulates this process.
心脏小梁化是一个关键的形态发生过程,在此过程中,心室心肌细胞簇伸出并扩展到心脏胶质中,形成片状突起。尽管有人提出心脏小梁可以增强心脏收缩力和室内传导,但它们在心脏发育中的确切功能尚未得到直接解决。我们发现,在斑马鱼 erbB2 突变体中,我们发现完全缺乏心脏小梁,心脏功能明显受损,突变体心脏表现出缩短分数降低和不成熟的传导模式。为了开始阐明 ErbB2 在心脏小梁化中的细胞机制,我们更仔细地分析了 erbB2 突变体心脏,并发现 ErbB2 活性的丧失导致小梁化阶段心肌细胞增殖完全缺失。此外,基于增殖、谱系追踪和移植研究获得的数据,我们提出心脏小梁化是由定向心肌细胞迁移而不是定向细胞分裂启动的,并且 ErbB2 自主调节这一过程。