{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:00:51Z","timestamp":1753884051244,"version":"3.41.2"},"reference-count":58,"publisher":"The Company of Biologists","issue":"2","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R00DE027218","R35DE027550"],"award-info":[{"award-number":["R00DE027218","R35DE027550"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["RGPIN-2014-06311"],"award-info":[{"award-number":["RGPIN-2014-06311"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The regulated expansion of chondrocytes within growth plates and joints ensures proper skeletal development through adulthood. Mutations in the transcription factor NKX3.2 underlie spondylo-megaepiphyseal-metaphyseal dysplasia (SMMD), which is characterized by skeletal defects including scoliosis, large epiphyses, wide growth plates and supernumerary distal limb joints. Whereas nkx3.2 knockdown zebrafish and mouse Nkx3.2 mutants display embryonic lethal jaw joint fusions and skeletal reductions, respectively, they lack the skeletal overgrowth seen in SMMD patients. Here, we report adult viable nkx3.2 mutant zebrafish displaying cartilage overgrowth in place of a missing jaw joint, as well as severe dysmorphologies of the facial skeleton, skullcap and spine. In contrast, cartilage overgrowth and scoliosis are absent in rare viable nkx3.2 knockdown animals that lack jaw joints, supporting post-embryonic roles for Nkx3.2. Single-cell RNA-sequencing and in vivo validation reveal increased proliferation and upregulation of stress-induced pathways, including prostaglandin synthases, in mutant chondrocytes. By generating a zebrafish model for the skeletal overgrowth defects of SMMD, we reveal post-embryonic roles for Nkx3.2 in dampening proliferation and buffering the stress response in joint-associated chondrocytes.<\/jats:p>","DOI":"10.1242\/dev.193409","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T16:41:04Z","timestamp":1610988064000},"source":"Crossref","is-referenced-by-count":8,"title":["Zebrafish model for spondylo-megaepiphyseal-metaphyseal dysplasia reveals post-embryonic roles of Nkx3.2 in the skeleton"],"prefix":"10.1242","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6126-2560","authenticated-orcid":false,"given":"Joanna","family":"Smeeton","sequence":"first","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"},{"name":"Columbia Stem Cell Initiative, Department of Rehabilitation and Regenerative Medicine, and Department of Genetics and Development, Columbia University Irving Medical Center, Columbia University, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arati","family":"Naveen Kumar","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0050-4594","authenticated-orcid":false,"given":"Tetsuto","family":"Miyashita","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada"},{"name":"Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0232-2022","authenticated-orcid":false,"given":"Pranidhi","family":"Baddam","sequence":"additional","affiliation":[{"name":"Department of Dentistry, University of Alberta, Edmonton, Alberta T6G 2R3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1096-6875","authenticated-orcid":false,"given":"Peter","family":"Fabian","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Graf","sequence":"additional","affiliation":[{"name":"Department of Dentistry, University of Alberta, Edmonton, Alberta T6G 2R3, Canada"},{"name":"Department of Medical Genetics, University of Alberta, Edmonton, Alberta T6G 2R7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3209-0026","authenticated-orcid":false,"given":"J. Gage","family":"Crump","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"key":"2021042623022291900_DEV193409C1","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.ydbio.2008.06.032","article-title":"Tri-phasic expression of posterior Hox genes during development of pectoral fins in zebrafish: implications for the evolution of vertebrate paired appendages","volume":"322","author":"Ahn","year":"2008","journal-title":"Dev. 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