The G protein-coupled receptor Agtrl1b regulates early development of myocardial progenitors
The G protein-coupled receptor Agtrl1b regulates early development of myocardial progenitors
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DOI：
10.1016/j.devcel.2007.01.012
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发表时间：
2007-03-01
影响因子：
11.8
通讯作者：
Stainier, Didier Y. R.
中科院分区：
文献类型：
--
作者：
Scott, Ian C.;Masri, Bernard;Stainier, Didier Y. R.
虽然已经确定了许多调节胚胎心脏形态发生和模式的因素，但对于调节注定形成心肌的祖细胞分化的分子事件知之甚少。在这里，我们发现斑马鱼grinch （gm）突变体形成心肌祖细胞数量减少，在最严重的情况下导致心肌细胞数量严重不足。我们发现gm编码G蛋白偶联受体（GPCR） Agtrl1b，这是一种已知的成人心血管生理调节因子。Apelin（一种Agtrl1b配体）的异位表达导致心肌细胞完全缺失。来自移植和转基因方法的数据表明，Agtrl1信号在心肌规范中起着细胞自主作用，其活性与原肠胚运动的开始一致。这些结果支持agtrl1b调节注定形成心肌祖细胞迁移的模型。
While many factors that modulate the morphogenesis and patterning of the embryonic heart have been identified, relatively little is known about the molecular events that regulate the differentiation of progenitor cells fated to form the myocardium. Here, we show that zebrafish grinch (gm) mutants form a reduced number of myocardial progenitor cells, which results in a profound deficit in cardiomyocyte numbers in the most severe cases. We show that gm encodes the G protein-coupled receptor (GPCR) Agtrl1b, a known regulator of adult cardiovascular physiology. Ectopic expression of Apelin, an Agtrl1b ligand, results in the complete absence of cardiomyocytes. Data from transplantation and transgenic approaches indicate that Agtrl1 signaling plays a cell-autonomous role in myocardial specification, with activity being required coincident with the onset of gastrulation movements. These results support a model in which agtrl1b regulates the migration of cells fated to form myocardial progenitors.