A dual role for ErbB2 signaling in cardiac trabeculation
A dual role for ErbB2 signaling in cardiac trabeculation
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DOI：
10.1242/dev.053736
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发表时间：
2010-11-15
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：
Liu, Jiandong;Bressan, Michael;Stainier, Didier Y. R.
心脏小梁形成是一个重要的形态发生过程，心室心肌细胞团挤压并扩张到心脏果冻中形成片状突起。虽然有研究表明，心小梁可增强心脏收缩力和心室传导，但其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，突变心脏表现出减少的部分缩短和不成熟的传导模式。为了开始阐明ErbB2在心脏小梁中功能的细胞机制，我们更仔细地分析了ErbB2突变心脏，发现ErbB2活性的丧失导致小梁阶段心肌细胞增殖完全缺失。此外，基于从增殖、谱系追踪和移植研究中获得的数据，我们提出心脏小梁是由定向心肌细胞迁移而不是定向细胞分裂引发的，ErbB2细胞自主调节这一过程。
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.