Title

Specific Requirement of Gli Transcription Factors in Hedgehog-mediated Intestinal Development

UMMS Affiliation

Department of Cancer Biology; Program in Gene Function and Expression; MassBiologics

Date

6-14-2013

Document Type

Article

Medical Subject Headings

Hedgehog Proteins; Oncogene Proteins; Trans-Activators; Intestines

Disciplines

Biochemistry, Biophysics, and Structural Biology | Cancer Biology | Developmental Biology

Abstract

Hedgehog (Hh) signaling is involved in multiple aspects of embryonic gut development, including mesenchymal growth and smooth muscle differentiation. The Gli family transcription factors is thought to collectively mediate Hh signaling in mammals. However, the function of different Gli proteins in gut development remains uncharacterized. Here, we genetically dissect the contribution of Gli transcriptional activation and de-repression in intestinal growth and patterning. We find that removal of the Gli3 repressor is dispensable for intestinal development and does not play a major role in Hh-controlled gut development. However, Gli2 activation is able to fully rescue the Smoothened (Smo)-null intestinal phenotype, suggesting that the Gli2 transcription factor is the main effector for Hh signaling in the intestine. To understand further the molecular mechanism underlying Hh/Gli function in the developing gut, we identify a subset of small leucine-rich glycoproteins (SLRPs) that may function downstream of Hh signaling in the mesenchyme. We show that osteoglycin, a SLRP, inhibits Hh-induced differentiation toward the smooth muscle lineage in C3H10T1/2 pluripotent mesenchymal cells. Taken together, our study reveals, for the first time, the distinct roles of Gli proteins in intestine development and suggests SLRPs as novel regulators of smooth muscle cell differentiation.

Rights and Permissions

Citation: J Biol Chem. 2013 Jun 14;288(24):17589-96. doi: 10.1074/jbc.M113.467498. Link to article on publisher's website

Related Resources

Link to article in PubMed

PubMed ID

23645682