Department of Biology, Nippon Medical School, Nakahara-ku, Kawasaki, Kanagawa, Japan.
Dev Dyn. 2012 Feb;241(2):403-14. doi: 10.1002/dvdy.23723. Epub 2011 Dec 20.
During Xenopus laevis metamorphosis, Sonic hedgehog (Shh) is directly induced by thyroid hormone (TH) at the transcription level as one of the earliest events in intestinal remodeling. However, the regulation of other components of this signaling pathway remains to be analyzed. Here, we analyzed the spatiotemporal expression of Patched (Ptc)-1, Smoothened (Smo), Gli1, Gli2, and Gli3 during natural and TH-induced intestinal remodeling.
We show that all of the genes examined are transiently up-regulated in the mesenchymal tissues during intestinal metamorphosis.
Interestingly, in the presence of protein synthesis inhibitors, Gli2 but not the others was induced by TH, suggesting that Gli2 is a direct TH response gene, while the others are likely indirect ones. Furthermore, we demonstrate by the organ culture experiment that overexpression of Shh enhances the expression of Ptc-1, Smo, and Glis even in the absence of TH, indicating that Shh regulates its own pathway components during intestinal remodeling.
在非洲爪蟾的变态过程中, Sonic hedgehog(Shh)作为肠道重塑的最早事件之一,在转录水平上直接被甲状腺激素(TH)诱导。然而,这个信号通路的其他成分的调节仍有待分析。在这里,我们分析了 Patched(Ptc)-1、Smoothened(Smo)、Gli1、Gli2 和 Gli3 在自然和 TH 诱导的肠道重塑过程中的时空表达。
我们表明,在肠道变态过程中,所有检测到的基因都在间充质组织中短暂上调。
有趣的是,在存在蛋白质合成抑制剂的情况下,只有 Gli2 而不是其他基因被 TH 诱导,这表明 Gli2 是一个直接的 TH 反应基因,而其他基因则可能是间接的。此外,我们通过器官培养实验证明,Shh 的过表达即使在没有 TH 的情况下也能增强 Ptc-1、Smo 和 Glis 的表达,表明 Shh 在肠道重塑过程中调节其自身途径的组成部分。