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The Mps one binder kinase activator (MOB) adaptor proteins are core components of Hippo signaling and influence Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which are potent transcriptional regulators. YAP1\/TAZ are key contributors to cartilage and bone development but the molecular mechanisms by which the Hippo pathway controls chondrogenesis are largely unknown. Cartilage is rich in ECM and also subject to strong external forces \u2013 two upstream factors regulating Hippo signaling. Chondrogenesis and endochondral ossification are tightly controlled by growth factors, morphogens, hormones, and transcriptional factors that engage in crosstalk with Hippo-YAP1\/TAZ signaling. Here, we generated tamoxifen-inducible, chondrocyte-specific Mob1a\/b-deficient mice and show that hyperactivation of endogenous YAP1\/TAZ impairs chondrocyte proliferation and differentiation\/maturation, leading to chondrodysplasia. These defects were linked to suppression of SOX9, a master regulator of chondrogenesis, the expression of which is mediated by TEAD transcription factors. Our data indicate that a MOB1-dependent YAP1\/TAZ-TEAD complex functions as a transcriptional repressor of SOX9 and thereby negatively regulates chondrogenesis.<\/jats:p>","DOI":"10.1242\/dev.159244","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T01:10:22Z","timestamp":1520385022000},"source":"Crossref","is-referenced-by-count":73,"title":["Loss of <i>Mob1a\/b<\/i> in mice results in chondrodysplasia due to YAP1\/TAZ-TEAD-dependent repression of SOX9"],"prefix":"10.1242","volume":"145","author":[{"given":"Hiroki","family":"Goto","sequence":"first","affiliation":[{"name":"Medical Institute of Bioregulation, Kyushu University 1 Division of Cancer Genetics , , Fukuoka 812-8582 , Japan"},{"name":"Kobe University Graduate School of Medicine 2 Division of Molecular and Cellular Biology , , Kobe, Hyogo 650-0017 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Nishio","sequence":"additional","affiliation":[{"name":"Medical Institute of Bioregulation, Kyushu University 1 Division of Cancer Genetics , , Fukuoka 812-8582 , Japan"},{"name":"Kobe University Graduate School of Medicine 2 Division of Molecular and Cellular Biology , , Kobe, Hyogo 650-0017 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7980-7186","authenticated-orcid":false,"given":"Yoko","family":"To","sequence":"additional","affiliation":[{"name":"Medical Institute of Bioregulation, Kyushu University 1 Division of Cancer Genetics , , Fukuoka 812-8582 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0371-1866","authenticated-orcid":false,"given":"Tatsuya","family":"Oishi","sequence":"additional","affiliation":[{"name":"Medical Institute of Bioregulation, Kyushu University 1 Division of Cancer Genetics , , Fukuoka 812-8582 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Miyachi","sequence":"additional","affiliation":[{"name":"Medical Institute of Bioregulation, Kyushu University 1 Division of Cancer Genetics , , Fukuoka 812-8582 , Japan"},{"name":"Kobe University Graduate School of Medicine 2 Division of Molecular and Cellular Biology , , Kobe, Hyogo 650-0017 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Maehama","sequence":"additional","affiliation":[{"name":"Kobe University Graduate School of Medicine 2 Division of Molecular and Cellular Biology , , Kobe, Hyogo 650-0017 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nishina","sequence":"additional","affiliation":[{"name":"Medical Research Institute, Tokyo Medical and Dental University 3 Department of Developmental and Regenerative Biology , , Tokyo 113-8510 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiko","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Gifu University School of Medicine 4 Department of Orthopaedic Surgery , , Gifu 501-1194 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tak Wah","family":"Mak","sequence":"additional","affiliation":[{"name":"Campbell Family Institute for Breast Cancer Research at the Princess Margaret Cancer Centre, University Health Network, 5 \u2008 Toronto M5G 2C1 , Canada ; Department of Medical Biophysics , , Toronto M5G 2C1 , Canada"},{"name":"University of Toronto, University Health Network 5 \u2008 Toronto M5G 2C1 , Canada ; Department of Medical Biophysics , , Toronto M5G 2C1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuma","family":"Makii","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Tokyo 6 Department of Sensory and Motor System Medicine , , Tokyo 113-8655 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Saito","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Tokyo 6 Department of Sensory and Motor System Medicine , , Tokyo 113-8655 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Yasoda","sequence":"additional","affiliation":[{"name":"Kyoto University Graduate School of Medicine 7 Department of Diabetes, Endocrinology and Nutrition , , Kyoto 606-8501 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Tsumaki","sequence":"additional","affiliation":[{"name":"Center for iPS Cell Research and Application, Kyoto University 8 Department of Cell Growth and Differentiation , , Kyoto 606-8507 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5950-8808","authenticated-orcid":false,"given":"Akira","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Medical Institute of Bioregulation, Kyushu University 1 Division of Cancer Genetics , , Fukuoka 812-8582 , Japan"},{"name":"Kobe University Graduate School of Medicine 2 Division of Molecular and Cellular Biology , , Kobe, Hyogo 650-0017 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2018,3,16]]},"reference":[{"key":"2024061223520432100_DEV159244C1","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3109\/s10165-008-0048-x","article-title":"Control of chondrogenesis by the transcription factor Sox9","volume":"18","author":"Akiyama","year":"2008","journal-title":"Mod. 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