Thyroid hormone-induced sonic hedgehog signal up-regulates its own pathway in a paracrine manner in the Xenopus laevis intestine during metamorphosis

Dev Dyn. 2012 Feb;241(2):403-14. doi: 10.1002/dvdy.23723. Epub 2011 Dec 20.

Abstract

Background: 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.

Results: We show that all of the genes examined are transiently up-regulated in the mesenchymal tissues during intestinal metamorphosis.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hedgehog Proteins / biosynthesis*
  • Intestinal Mucosa / metabolism
  • Intestines / growth & development*
  • Kruppel-Like Transcription Factors / biosynthesis
  • Metamorphosis, Biological / drug effects
  • Metamorphosis, Biological / physiology*
  • Oncogene Proteins / biosynthesis
  • Paracrine Communication
  • Receptors, Cell Surface / biosynthesis
  • Repressor Proteins / biosynthesis
  • Smoothened Receptor
  • Thyroid Hormones / metabolism*
  • Thyroid Hormones / pharmacology
  • Trans-Activators / biosynthesis
  • Up-Regulation
  • Xenopus Proteins / biosynthesis
  • Xenopus laevis / growth & development*
  • Xenopus laevis / metabolism
  • Zinc Finger Protein GLI1
  • Zinc Finger Protein Gli2
  • Zinc Finger Protein Gli3

Substances

  • GLI3 protein, Xenopus
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors
  • Oncogene Proteins
  • PTCH1 protein, Xenopus
  • Receptors, Cell Surface
  • Repressor Proteins
  • Smo protein, Xenopus
  • Smoothened Receptor
  • Thyroid Hormones
  • Trans-Activators
  • Xenopus Proteins
  • Zinc Finger Protein GLI1
  • Zinc Finger Protein Gli2
  • Zinc Finger Protein Gli3