Extracardiac control of embryonic cardiomyocyte proliferation and ventricular wall expansion
Extracardiac control of embryonic cardiomyocyte proliferation and ventricular wall expansion
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DOI：
10.1093/cvr/cvu269
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发表时间：
2015-03-01
影响因子：
10.8
通讯作者：
Sucov, Henry M.
中科院分区：
文献类型：
--
作者：
Shen, Hua;Cavallero, Susana;Sucov, Henry M.
在心脏发育过程中控制心室壁形成的策略还不清楚。在以前的研究中，我们记录了IGF2作为控制心室心肌细胞增殖和室壁扩张的主要促有丝分裂信号。本研究的目的是确定心脏发育过程中IGF 2的组织来源以及控制其表达的上游途径，并利用多种小鼠遗传学工具证实IGF 2的关键来源是心外膜。我们发现，心外膜Igf2的表达控制在一个双相的方式，首先诱导红细胞生成素，然后调节氧气和葡萄糖与胎盘功能的发病。这两个过程都是由视黄酸信号独立控制的。我们的研究结果表明，心室壁心肌细胞增殖分为不同的调节阶段。每一个都涉及来自心脏外部的指导性线索，从而以内分泌方式作用于心外膜，这是一种在胚胎发生中大多数未知的调节模式。
The strategies that control formation of the ventricular wall during heart development are not well understood. In previous studies, we documented IGF2 as a major mitogenic signal that controls ventricular cardiomyocyte proliferation and chamber wall expansion. Our objective in this study was to define the tissue source of IGF2 in heart development and the upstream pathways that control its expression.Using a number of mouse genetic tools, we confirm that the critical source of IGF2 is the epicardium. We find that epicardial Igf2 expression is controlled in a biphasic manner, first induced by erythropoietin and then regulated by oxygen and glucose with onset of placental function. Both processes are independently controlled by retinoic acid signalling.Our results demonstrate that ventricular wall cardiomyocyte proliferation is subdivided into distinct regulatory phases. Each involves instructive cues that originate outside the heart and thereby act on the epicardium in an endocrine manner, a mode of regulation that is mostly unknown in embryogenesis.