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Although rare, IS with onset during infancy is the more severe and rapidly progressive form of the disease, associated with increased mortality due to significant respiratory compromise. The pathophysiology of IS, in particular for infantile IS, remains elusive. Here, we demonstrate the role of PRMT5 in the infantile IS phenotype in mouse. Conditional genetic ablation of PRMT5 in osteochondral progenitors results in impaired terminal hypertrophic chondrocyte differentiation and asymmetric defects of endochondral bone formation in the perinatal spine. Analysis of these several markers of endochondral ossification revealed increased type X collagen (COLX) and Ihh expression, coupled with a dramatic reduction in Mmp13 and RUNX2 expression, in the vertebral growth plate and in regions of the intervertebral disc in the Prmt5 conditional mutant mice. We also demonstrate that PRMT5 has a continuous role in the intervertebral disc and vertebral growth plate in adult mice. Altogether, our results establish PRMT5 as a critical promoter of terminal hypertrophic chondrocyte differentiation and endochondral bone formation during spine development and homeostasis.<\/jats:p>\n                  <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/dmm.041251","type":"journal-article","created":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T14:55:11Z","timestamp":1576594511000},"source":"Crossref","is-referenced-by-count":19,"title":["Regulation of terminal hypertrophic chondrocyte differentiation in\n                    <i>Prmt5<\/i>\n                    mutant mice modeling infantile idiopathic scoliosis"],"prefix":"10.1242","volume":"12","author":[{"given":"Zhaoyang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd, The University of Texas at Austin, Dell Medical School, Austin, TX 78723, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janani","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, 2500 Speedway, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven A.","family":"Vokes","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, 2500 Speedway, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9668-6497","authenticated-orcid":false,"given":"Ryan S.","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd, The University of Texas at Austin, Dell Medical School, Austin, TX 78723, USA"},{"name":"Department of Nutritional Sciences, 200 W 24th Street, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2019,12,17]]},"reference":[{"key":"2021042700233578300_DMM041251C1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41413-018-0021-z","article-title":"The art of building bone: emerging role of chondrocyte-to-osteoblast transdifferentiation in endochondral ossification","volume":"6","author":"Aghajanian","year":"2018","journal-title":"Bone Res."},{"key":"2021042700233578300_DMM041251C2","doi-asserted-by":"publisher","first-page":"2813","DOI":"10.1101\/gad.1017802","article-title":"The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6","volume":"16","author":"Akiyama","year":"2002","journal-title":"Genes Dev."},{"key":"2021042700233578300_DMM041251C3","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.devcel.2011.04.018","article-title":"Overlapping roles and collective requirement for the coreceptors GAS1, CDO, and BOC in SHH pathway function","volume":"20","author":"Allen","year":"2011","journal-title":"Dev. 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