title: Specific requirement of Gli transcription factors in Hedgehog-mediated intestinal development.
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.
authors: Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors: He
authors: H
authors: Huang
authors: Jennifer L
authors: JL
authors: Cotton
authors: Yang
authors: Y
authors: Wang
authors: Mihir
authors: M
authors: Rajurkar
authors: Lihua J
authors: LJ
authors: Zhu
authors: Brian C
authors: BC
authors: Lewis
authors: Junhao
authors: J
authors: Mao
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000196:embryology*; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D008648:Mesoderm / Q000196:embryology; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000072086:Smoothened Receptor; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
chemical_list: C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; C512906:Ogn protein, mouse; D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
keywords: Development; Embryo; Gli; Hedgehog; Intestine; Mesenchyme; Signaling
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