BOP, a regulator of right ventricular heart development, is a direct transcriptional target of MEF2C in the developing heart
BOP, a regulator of right ventricular heart development, is a direct transcriptional target of MEF2C in the developing heart
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DOI：
10.1242/dev.01849
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发表时间：
2005-06-01
期刊：
影响因子：
4.6
通讯作者：
Olson, EN
中科院分区：
文献类型：
--
作者：
Phan, D;Rasmussen, TL;Olson, EN
脊椎动物心脏在胚胎发生期间以模块化方式从不同的前体细胞群体组装。右心室腔和流出道主要来源于称为前心野的祖细胞群。这些区域的心脏是严重发育不全的突变小鼠缺乏的肌细胞增强因子2C（MEF 2C）和BOP转录因子，这表明这些心源性调节因子可能在一个共同的途径，为发展的前心脏领域及其衍生物。我们表明，在发展中的心脏Bop的表达依赖于MEF 2C的直接结合MEF 2-响应元件的Bop启动子，这是必要的和足够的重演内源性Bop的表达在前心脏领域和其心脏衍生物在小鼠的发展。Bop启动子也指导骨骼肌谱系中的转录，但只有心脏表达依赖于MEF 2。这些研究结果确定Bop作为MEF 2C在发育中心脏的重要下游效应基因，并揭示了参与前心区及其衍生物发育的转录级联反应。
The vertebrate heart is assembled during embryogenesis in a modular manner from different populations of precursor cells. The right ventricular chamber and outflow tract are derived primarily from a population of progenitors known as the anterior heart field. These regions of the heart are severely hypoplastic in mutant mice lacking the myocyte enhancer factor 2C (MEF2C) and BOP transcription factors, suggesting that these cardiogenic regulatory factors may act in a common pathway for development of the anterior heart field and its derivatives. We show that Bop expression in the developing heart depends on the direct binding of MEF2C to a MEF2-response element in the Bop promoter that is necessary and sufficient to recapitulate endogenous Bop expression in the anterior heart field and its cardiac derivatives during mouse development. The Bop promoter also directs transcription in the skeletal muscle lineage, but only cardiac expression is dependent on MEF2. These findings identify Bop as an essential downstream effector gene of MEF2C in the developing heart, and reveal a transcriptional cascade involved in development of the anterior heart field and its derivatives.