Evidence for the involvement of the Gli gene family in embryonic mouse lung development
Evidence for the involvement of the Gli gene family in embryonic mouse lung development
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DOI：
10.1006/dbio.1997.8644
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发表时间：
1997-08-15
影响因子：
2.7
通讯作者：
Hogan, BLM
中科院分区：
文献类型：
--
作者：
Grindley, JC;Bellusci, S;Hogan, BLM
小鼠 Gli、Gli2 和 Gli3 是与果蝇 cubitus interuptus 相关的锌指基因，是刺猬信号转导途径的一个组成部分。在胚胎肺中，所有三个 Gli 基因在假腺体阶段（中胚层的不同但重叠的区域）强烈表达。随后，Gli 和 Gli3（而非 Gli2）的表达在小管阶段下调，与声波刺猬 (Shh) 和刺猬受体基因 patched (Ptc) 表达的下降一致。肺部中 Shh 的过度表达会导致 Ptc mRNA 水平升高。 Gli（而非 Gli2）也上调，表明 Gli 基因在肺发育过程中对 SHH 对 Ptc 的调节有不同的参与。 Gli3 不会因 Shh 过度表达而上调。然而，Gli3（XtJ）胚胎（涉及 Gli3 基因缺失的突变纯合子）的发现显示了其对肺发育的重要性，其肺形态发生具有典型的异常模式。这些胚胎中的肺部缺陷包括局部形状变化和尺寸减小，与正常的 Gli3 表达相关。因此，我们的数据表明，Gli 基因之一，Gli3，对于正常的肺部发育至关重要，而另一个基因，Gli，可以放置在肺部 Shh 信号传导的下游。 (C) 1997 年学术出版社。
Murine Gli, Gli2, and Gli3 are zinc finger genes related to Drosophila cubitus interuptus, a component of the hedgehog signal transduction pathway. In the embryonic lung, all three Gli genes are strongly expressed at the pseudoglandular stage, in distinct but overlapping domains of the mesoderm. Expression of Gli and Gli3, but not of Gli2, is subsequently downregulated at the canalicular stage, coincident with a decline in the expression of sonic hedgehog (Shh) and the hedgehog receptor gene, patched (Ptc). Overexpression of Shh in the lung results in increased levels of Ptc mRNA. Gli, but not Gli2, is also upregulated, suggesting a differential involvement of the Gli genes in the regulation of Ptc by SHH during lung development. Gli3 is not upregulated by Shh overexpression. However, its importance for lung development is shown by the finding that Gli3(XtJ) embryos, homozygous for a mutation involving a deletion of the Gli3 gene, have a stereotypic pattern of abnormalities in lung morphogenesis. The pulmonary defects in these embryos, consisting of localized shape changes and size reductions, correlate with normal Gli3 expression. Thus, our data indicate that one of the Gli genes, Gli3, is essential for normal lung development, and that another, Gli, can be placed downstream of Shh signaling in the lung. (C) 1997 Academic Press.