BACKGROUND The embryonic day E10-13 period of mouse heart development is characterized by robust cardiomyocyte proliferation that creates the compact zone of thickened ventricular wall myocardium. This process is initiated by the formation of the epicardium on the outer heart surface, which releases insulin-like growth factor 2 (IGF2) as the primary cardiomyocyte mitogen. Two receptors mediate IGF2 signaling, the IGF1R and the insulin receptor (INSR). RESULTS In this study, we addressed the relative roles of the two IGF2 receptors in mouse heart development. We find that both receptors are expressed in the mouse heart during the E10-13 period, although IGF1R is much more prominently activated by IGF2 than INSR. Genetic manipulation indicates that only Igf1r is required for embryonic ventricular wall morphogenesis. INSR is not hyperactivated in the absence of IGF1R, and INSR does not compensate functionally for IGF1R in the absence of the latter. CONCLUSIONS These results define the molecular components that are responsible for a major burst of cardiomyocyte proliferation during heart development. These results may also be relevant to understanding the efficiency of regeneration of the mammalian heart after neonatal and adult injury.

中文翻译：

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胰岛素样生长因子 1 受体和胰岛素受体在胚胎心脏发育过程中的不同作用。

背景技术小鼠心脏发育的胚胎期 E10-13 期的特点是心肌细胞增殖旺盛，从而产生了增厚的心室壁心肌的致密区。这个过程是由心外膜在心脏外表面的形成开始的，心外膜释放胰岛素样生长因子 2 (IGF2) 作为主要的心肌细胞有丝分裂原。两种受体介导 IGF2 信号传导，IGF1R 和胰岛素受体 (INSR)。结果 在这项研究中，我们探讨了两种 IGF2 受体在小鼠心脏发育中的相对作用。我们发现这两种受体在 E10-13 期间都在小鼠心脏中表达，尽管 IGF1R 比 INSR 更显着地被 IGF2 激活。基因操作表明胚胎心室壁形态发生只需要 Igf1r。在没有 IGF1R 的情况下，INSR 不会过度激活，并且在没有 IGF1R 的情况下，INSR 不会在功能上补偿 IGF1R。结论 这些结果定义了导致心脏发育过程中心肌细胞增殖的主要爆发的分子成分。这些结果也可能与了解哺乳动物心脏在新生儿和成人受伤后的再生效率有关。