{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:48:46Z","timestamp":1787021326533,"version":"build-2736575974"},"reference-count":105,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":503,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010438","name":"Francis Crick Institute","doi-asserted-by":"publisher","award":["FC001180"],"award-info":[{"award-number":["FC001180"]}],"id":[{"id":"10.13039\/100010438","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["FC001180"],"award-info":[{"award-number":["FC001180"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Council","award":["FC001180"],"award-info":[{"award-number":["FC001180"]}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["FC001180"],"award-info":[{"award-number":["FC001180"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000995","name":"Australian National University","doi-asserted-by":"publisher","award":["R4210005"],"award-info":[{"award-number":["R4210005"]}],"id":[{"id":"10.13039\/501100000995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The Hippo-YAP\/TAZ pathway is an important regulator of tissue growth, but can also control cell fate or tissue morphogenesis. Here we investigate the function of the Hippo pathway during the development of cartilage, which forms the majority of the skeleton. Previously, YAP was proposed to inhibit skeletal size by repressing chondrocyte proliferation and differentiation. We find that, in vitro, Yap\/Taz double knockout impairs chondrocyte proliferation, whilst constitutively nuclear nls-YAP5SA accelerates proliferation, in line with the canonical role of this pathway in most tissues. However, in vivo, cartilage-specific knockout of Yap\/Taz does not prevent chondrocyte proliferation, differentiation, or skeletal growth, but rather results in various skeletal deformities including cleft palate. Cartilage-specific expression of nls-YAP5SA or knockout of Lats1\/2 do not increase cartilage growth but instead lead to catastrophic malformations resembling chondrodysplasia or achondrogenesis. Physiological YAP target genes in cartilage include Ctgf, Cyr61 and several matrix remodelling enzymes. Thus, YAP\/TAZ activity controls chondrocyte proliferation in vitro, possibly reflecting a regenerative response, but is dispensable for chondrocyte proliferation in vivo, and instead functions to control cartilage morphogenesis via regulation of the extracellular matrix.<\/jats:p>","DOI":"10.1242\/dev.187187","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T14:01:19Z","timestamp":1601388079000},"source":"Crossref","is-referenced-by-count":33,"title":["Control of skeletal morphogenesis by the Hippo-YAP\/TAZ pathway"],"prefix":"10.1242","author":[{"given":"Hannah K.","family":"Vanyai","sequence":"first","affiliation":[{"name":"The Francis Crick Institute, 1 Midland Rd, St Pancras, NW1 1AT, London, United Kingdom"},{"name":"Current address: The Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, 3052, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Prin","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, 1 Midland Rd, St Pancras, NW1 1AT, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriane","family":"Guillermin","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, 1 Midland Rd, St Pancras, NW1 1AT, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishara","family":"Marzook","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, 1 Midland Rd, St Pancras, NW1 1AT, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Boeing","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, 1 Midland Rd, St Pancras, NW1 1AT, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Howson","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, 1 Midland Rd, St Pancras, NW1 1AT, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca E.","family":"Saunders","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, 1 Midland Rd, St Pancras, NW1 1AT, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Snoeks","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, 1 Midland Rd, St Pancras, NW1 1AT, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Howell","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, 1 Midland Rd, St Pancras, NW1 1AT, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0216-0417","authenticated-orcid":false,"given":"Timothy J.","family":"Mohun","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, 1 Midland Rd, St Pancras, NW1 1AT, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0103-040X","authenticated-orcid":false,"given":"Barry","family":"Thompson","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, 1 Midland Rd, St Pancras, NW1 1AT, London, United Kingdom"},{"name":"EMBL Australia, Department of Cancer Biology & Therapeutics, The John Curtin School of Medical Research, The Australian National University, Garran Rd, Acton, 2601, Canberra, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2021042700562119100_DEV187187C1","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":"2021042700562119100_DEV187187C2","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1101\/gad.1171104","article-title":"Interactions between Sox9 and beta-catenin control chondrocyte differentiation","volume":"18","author":"Akiyama","year":"2004","journal-title":"Genes Dev."},{"key":"2021042700562119100_DEV187187C3","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1042\/BJ20081991","article-title":"N-terminal domains of CCN family 2\/connective tissue growth factor bind to aggrecan","volume":"420","author":"Aoyama","year":"2009","journal-title":"Biochem. 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