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U.S.A."],"published-print":{"date-parts":[[2022,11,29]]},"abstract":"<jats:p>The shaping of bone structures relies on various cell types and signaling pathways. Here, we use the zebrafish bifurcating fin rays during regeneration to investigate bone patterning. We found that the regenerating fin rays form via two mineralization fronts that undergo an osteoblast-dependent fusion\/stitching until the branchpoint, and that bifurcation is not simply the splitting of one unit into two. We identified tartrate-resistant acid phosphatase-positive osteolytic tubular structures at the branchpoints, hereafter named osteolytic tubules (OLTs). Chemical inhibition of their bone-resorbing activity strongly impairs ray bifurcation, indicating that OLTs counteract the stitching process. Furthermore, by testing different osteoactive compounds, we show that the position of the branchpoint depends on the balance between bone mineralization and resorption activities. Overall, these findings provide a unique perspective on fin ray formation and bifurcation, and reveal a key role for OLTs in defining the proximo-distal position of the branchpoint.<\/jats:p>","DOI":"10.1073\/pnas.2209231119","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T18:40:57Z","timestamp":1669228857000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Fin ray branching is defined by TRAP\n            <sup>+<\/sup>\n            osteolytic tubules in zebrafish"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3722-8810","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Cardeira-da-Silva","sequence":"first","affiliation":[{"name":"Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany"},{"name":"DZHK-German Centre for Cardiovascular Research, Partner Site Rhine-Main, 61231 Bad Nauheim, Germany"},{"name":"CCMAR-Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1663-2232","authenticated-orcid":false,"given":"Anabela","family":"Bensimon-Brito","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany"},{"name":"DZHK-German Centre for Cardiovascular Research, Partner Site Rhine-Main, 61231 Bad Nauheim, Germany"},{"name":"INSERM-National Institute of Health and Medical Research, Atip-Avenir, Aix Marseille University, Marseille Medical Genetics, 13005 Marseille, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5894-6526","authenticated-orcid":false,"given":"Marco","family":"Tarasco","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany"},{"name":"CCMAR-Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5842-033X","authenticated-orcid":false,"given":"Ana S.","family":"Brand\u00e3o","sequence":"additional","affiliation":[{"name":"CEDOC-Chronic Diseases Research Center, NOVA Medical School, NOVA University of Lisbon, 1150-082 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7947-2681","authenticated-orcid":false,"given":"Joana T.","family":"Rosa","sequence":"additional","affiliation":[{"name":"CCMAR-Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal"}]},{"given":"Jorge","family":"Borbinha","sequence":"additional","affiliation":[{"name":"CEDOC-Chronic Diseases Research Center, NOVA Medical School, NOVA University of Lisbon, 1150-082 Lisbon, Portugal"}]},{"given":"Paulo J.","family":"Almeida","sequence":"additional","affiliation":[{"name":"STAB VIDA-Investiga\u00e7\u00e3o e Servi\u00e7os em Ci\u00eancias Biol\u00f3gicas, 2825-182 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4193-6089","authenticated-orcid":false,"given":"Ant\u00f3nio","family":"Jacinto","sequence":"additional","affiliation":[{"name":"CEDOC-Chronic Diseases Research Center, NOVA Medical School, NOVA University of Lisbon, 1150-082 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3114-6662","authenticated-orcid":false,"given":"M. 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