{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T23:54:07Z","timestamp":1778111647151,"version":"3.51.4"},"reference-count":68,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["312217"],"award-info":[{"award-number":["312217"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>During zebrafish fin regeneration, blastema cells lining the epidermis differentiate into osteoblasts and joint cells to reconstruct the segmented bony rays. We show that osteoblasts and joint cells originate from a common cell lineage, but are committed to different cell fates. Pre-osteoblasts expressing runx2a\/b commit to the osteoblast lineage upon expressing sp7, while the strong upregulation of hoxa13a correlates with a commitment to a joint cell type. In the distal regenerate, hoxa13a, evx1, and pthlha are sequentially upregulated at regular intervals to define the newly identified presumptive joint cells. Presumptive joint cells mature into joint-forming cells, a distinct cell cluster that maintains the expression of these factors. Analysis of evx1 null mutants reveals that evx1 is acting upstream of pthlha and downstream or parallel to hoxa13a. Calcineurin activity, potentially through the inhibition of retinoic acid signaling, regulates evx1, pthlha, and hoxa13a expression during joint formation. Furthermore, retinoic acid treatment induces osteoblast differentiation in mature joint cells, leading to ectopic bone deposition in joint regions. Overall, our data reveal a novel regulatory pathway essential for joint formation in the regenerating fin.<\/jats:p>","DOI":"10.1242\/dev.161158","type":"journal-article","created":{"date-parts":[[2018,5,11]],"date-time":"2018-05-11T09:10:16Z","timestamp":1526029816000},"source":"Crossref","is-referenced-by-count":30,"title":["A regulatory pathway involving retinoic acid and calcineurin demarcates and maintains joint cells and osteoblasts in the fin regenerate"],"prefix":"10.1242","author":[{"given":"Stephanie C.","family":"McMillan","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Ottawa, ON, K1N 6N5, Canada"},{"name":"CAREG, 30 Marie Curie, University of Ottawa, ON, K1N 6N5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7105-2292","authenticated-orcid":false,"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAREG, 30 Marie Curie, University of Ottawa, ON, K1N 6N5, Canada"},{"name":"Department of Biology, 30 Marie Curie, University of Ottawa, ON, K1N 6N5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hue-Eileen","family":"Phan","sequence":"additional","affiliation":[{"name":"CAREG, 30 Marie Curie, University of Ottawa, ON, K1N 6N5, Canada"},{"name":"Department of Biology, 30 Marie Curie, University of Ottawa, ON, K1N 6N5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirine","family":"Jeradi","sequence":"additional","affiliation":[{"name":"Institute for Developmental Biology, Cologne University, Cologne, Germany"},{"name":"Institut Polytechnique priv\u00e9, universit\u00e9 libre de Tunis, Tunis, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6226-1060","authenticated-orcid":false,"given":"Leona","family":"Probst","sequence":"additional","affiliation":[{"name":"CAREG, 30 Marie Curie, University of Ottawa, ON, K1N 6N5, Canada"},{"name":"Department of Biology, 30 Marie Curie, University of Ottawa, ON, K1N 6N5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Hammerschmidt","sequence":"additional","affiliation":[{"name":"Institute for Developmental Biology, Cologne University, Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Andr\u00e9e","family":"Akimenko","sequence":"additional","affiliation":[{"name":"CAREG, 30 Marie Curie, University of Ottawa, ON, K1N 6N5, Canada"},{"name":"Department of Biology, 30 Marie Curie, University of Ottawa, ON, K1N 6N5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2018,1,1]]},"reference":[{"key":"2021042609145683100_DEV161158C1","doi-asserted-by":"publisher","first-page":"3133","DOI":"10.1242\/dev.002709","article-title":"Regulation of skeletogenic differentiation in cranial dermal bone","volume":"134","author":"Abzhanov","year":"2007","journal-title":"Development"},{"key":"2021042609145683100_DEV161158C2","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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