Grindley J C, Bellusci S, Perkins D, Hogan B L
Department of Cell Biology, Vanderbilt University Medical Center, Nashville, Tennessee, 37232-2175, USA.
Dev Biol. 1997 Aug 15;188(2):337-48. doi: 10.1006/dbio.1997.8644.
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 Gli3XtJ 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.
小鼠Gli、Gli2和Gli3是与果蝇分节基因（果蝇中刺猬信号转导途径的一个组成部分）相关的锌指基因。在胚胎肺中，所有这三个Gli基因在假腺期均在中胚层的不同但重叠区域强烈表达。随后，在小管期，Gli和Gli3的表达下调，但Gli2的表达未下调，这与音猬因子（Shh）和刺猬受体基因（patched，Ptc）的表达下降同时发生。肺中Shh的过表达导致Ptc mRNA水平升高。Gli（而非Gli2）也上调，这表明在肺发育过程中，Gli基因在SHH对Ptc的调控中存在差异参与。Gli3不会因Shh过表达而上调。然而，Gli3XtJ胚胎（Gli3基因缺失突变的纯合子）在肺形态发生中具有定型的异常模式，这一发现表明Gli3对肺发育很重要。这些胚胎中的肺部缺陷包括局部形状改变和尺寸减小，与正常的Gli3表达相关。因此，我们的数据表明，Gli基因之一Gli3对正常肺发育至关重要，而另一个基因Gli可位于肺中Shh信号传导的下游。
