Hes1 is expressed in the second heart field and is required for outflow tract development.

Hes1 is expressed in the second heart field and is required for outflow tract development.
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DOI:
10.1371/journal.pone.0006267
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发表时间:
2009-07-17
期刊:
影响因子:
3.7
通讯作者:
Kelly RG
Kelly RG
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Rochais F;Dandonneau M;Mesbah K;Jarry T;Mattei MG;Kelly RG

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通过将第二心脏区域的祖细胞添加到伸长的心脏管的两极,胚胎心脏会快速生长。这一过程的失败或干扰会导致先天性心脏缺陷。为了进一步了解第二心脏区的发育,我们表征了由于整合位点位置效应而在第二心脏区和流出道中表达的转基因的插入位点。在这里,我们表明 A17-Myf5-nlacZ-T55 转基因的整合位点位于 Hes1 的上游,编码一个基本螺旋-环-螺旋,其中含有胚胎发育过程中维持不同祖细胞群所需的转录抑制子。 Hes1 表达位点的子集(包括 CNS、咽上皮、心包、肢芽和肺内胚层)中的转基因表达表明 Hes1 是转基因捕获的调控元件的内源性靶标。 Hes1 在咽内胚层和中胚层(包括第二心区)中表达。对胚胎第 15.5 天的 Hes1 突变心脏的分析揭示了流出道排列缺陷,包括室间隔缺陷和主动脉。在早期发育阶段,Hes1突变胚胎表现出第二心脏区增殖缺陷、心脏神经嵴细胞减少以及未能完全延伸流出道。 Hes1 在早期胚胎的心脏祖细胞中表达,是心脏动脉极发育所必需的。
Rapid growth of the embryonic heart occurs by addition of progenitor cells of the second heart field to the poles of the elongating heart tube. Failure or perturbation of this process leads to congenital heart defects. In order to provide further insight into second heart field development we characterized the insertion site of a transgene expressed in the second heart field and outflow tract as the result of an integration site position effect. Here we show that the integration site of the A17-Myf5-nlacZ-T55 transgene lies upstream of Hes1, encoding a basic helix-loop-helix containing transcriptional repressor required for the maintenance of diverse progenitor cell populations during embryonic development. Transgene expression in a subset of Hes1 expression sites, including the CNS, pharyngeal epithelia, pericardium, limb bud and lung endoderm suggests that Hes1 is the endogenous target of regulatory elements trapped by the transgene. Hes1 is expressed in pharyngeal endoderm and mesoderm including the second heart field. Analysis of Hes1 mutant hearts at embryonic day 15.5 reveals outflow tract alignment defects including ventricular septal defects and overriding aorta. At earlier developmental stages, Hes1 mutant embryos display defects in second heart field proliferation, a reduction in cardiac neural crest cells and failure to completely extend the outflow tract. Hes1 is expressed in cardiac progenitor cells in the early embryo and is required for development of the arterial pole of the heart.
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