Hand2 ensures an appropriate environment for cardiac fusion by limiting Fibronectin function
Hand2 ensures an appropriate environment for cardiac fusion by limiting Fibronectin function
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DOI：
10.1242/dev.052225
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发表时间：
2010-10-01
期刊：
影响因子：
4.6
通讯作者：
Yelon, Deborah
中科院分区：
文献类型：
--
作者：
Garavito-Aguilar, Zayra V.;Riley, Heather E.;Yelon, Deborah
心脏的形成需要双侧心肌细胞群在向胚胎中线移动时融合。bHLH转录因子Hand2对心脏融合至关重要；然而，执行Hand2功能的效应基因是未知的。在这里，我们在斑马鱼中提供了Hand2通路下游成分介导心脏形态发生的第一个证据。虽然hand2在心肌细胞中表达，但镶嵌分析表明它在调节心肌细胞运动中起非自主作用。基因表达谱显示在hand2突变胚胎中纤维连接蛋白1 （fn1）的表达增加。反之，hand2过表达导致纤维连接蛋白水平降低。此外，fn1功能的降低可以挽救hand2突变体的心脏融合：双侧心肌细胞群合并并表现出改善的组织结构，尽管没有重大的尖基底极性变化。总之，我们的数据提供了一个组织为其形态发生创造有利环境的新例子：Hand2通路通过负调节Fn1水平为心脏融合建立了适当的环境。
Heart formation requires the fusion of bilateral cardiomyocyte populations as they move towards the embryonic midline. The bHLH transcription factor Hand2 is essential for cardiac fusion; however, the effector genes that execute this function of Hand2 are unknown. Here, we provide in zebrafish the first evidence for a downstream component of the Hand2 pathway that mediates cardiac morphogenesis. Although hand2 is expressed in cardiomyocytes, mosaic analysis demonstrates that it plays a non-autonomous role in regulating cardiomyocyte movement. Gene expression profiles reveal heightened expression of fibronectin 1 (fn1) in hand2 mutant embryos. Reciprocally, overexpression of hand2 leads to decreased Fibronectin levels. Furthermore, reduction of fn1 function enables rescue of cardiac fusion in hand2 mutants: bilateral cardiomyocyte populations merge and exhibit improved tissue architecture, albeit without major changes in apicobasal polarity. Together, our data provide a novel example of a tissue creating a favorable environment for its morphogenesis: the Hand2 pathway establishes an appropriate environment for cardiac fusion through negative modulation of Fn1 levels.