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dc.contributor.authorHuang, He
dc.contributor.authorCotton, Jennifer L.
dc.contributor.authorWang, Yang
dc.contributor.authorRajurkar, Mihir
dc.contributor.authorZhu, Lihua Julie
dc.contributor.authorLewis, Brian C.
dc.contributor.authorMao, Junhao
dc.date2022-08-11T08:10:15.000
dc.date.accessioned2022-08-23T17:01:27Z
dc.date.available2022-08-23T17:01:27Z
dc.date.issued2013-06-14
dc.date.submitted2013-07-02
dc.identifier.citationJ Biol Chem. 2013 Jun 14;288(24):17589-96. doi: 10.1074/jbc.M113.467498. <a href="http://dx.doi.org/10.1074/jbc.M113.467498">Link to article on publisher's website</a>
dc.identifier.issn1083-351X
dc.identifier.doi10.1074/jbc.M113.467498
dc.identifier.pmid23645682
dc.identifier.urihttp://hdl.handle.net/20.500.14038/44009
dc.description.abstractHedgehog (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.
dc.language.isoen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=23645682&dopt=Abstract">Link to article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1074/jbc.M113.467498
dc.subjectHedgehog Proteins
dc.subjectOncogene Proteins
dc.subjectTrans-Activators
dc.subjectIntestines
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectCancer Biology
dc.subjectDevelopmental Biology
dc.titleSpecific Requirement of Gli Transcription Factors in Hedgehog-mediated Intestinal Development
dc.typeArticle
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume288
dc.source.issue24
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/pgfe_pp/216
dc.identifier.contextkey4277324
html.description.abstract<p>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.</p>
dc.identifier.submissionpathpgfe_pp/216
dc.contributor.departmentMassBiologics
dc.contributor.departmentProgram in Gene Function and Expression
dc.contributor.departmentDepartment of Cancer Biology
dc.source.pages17589-96


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