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Zebrafish naturally heal large injuries to mandibular bone, offering an opportunity to understand how to boost intrinsic healing potential. Using a novel her6:mCherry Notch reporter, we show that canonical Notch signaling is induced during the initial stages of cartilage callus formation in both mesenchymal cells and chondrocytes following surgical mandibulectomy. We also show that modulation of Notch signaling during the initial post-operative period results in lasting changes to regenerate bone quantity one month later. Pharmacological inhibition of Notch signaling reduces the size of the cartilage callus and delays its conversion into bone, resulting in non-union. Conversely, conditional transgenic activation of Notch signaling accelerates conversion of the cartilage callus into bone, improving bone healing. Given the conserved functions of this pathway in bone repair across vertebrates, we propose that targeted activation of Notch signaling during the early phases of bone healing in mammals may both augment the size of the initial callus and boost its ossification into reparative bone.<\/jats:p>","DOI":"10.1242\/dev.199995","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T09:26:09Z","timestamp":1645176369000},"source":"Crossref","is-referenced-by-count":26,"title":["Notch signaling enhances bone regeneration in the zebrafish mandible"],"prefix":"10.1242","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7890-0613","authenticated-orcid":false,"given":"Jessica M.","family":"Kraus","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dion","family":"Giovannone","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Rydzik","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1852-8749","authenticated-orcid":false,"given":"Jeremy L.","family":"Balsbaugh","sequence":"additional","affiliation":[{"name":"Proteomics & Metabolomics Facility, Center for Open Research Resources & Equipment, University of Connecticut, Storrs, CT 06269, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac L.","family":"Moss","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Schwedler","sequence":"additional","affiliation":[{"name":"Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6570-4082","authenticated-orcid":false,"given":"Julien Y.","family":"Bertrand","sequence":"additional","affiliation":[{"name":"Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9652-7653","authenticated-orcid":false,"given":"David","family":"Traver","sequence":"additional","affiliation":[{"name":"Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6361-143X","authenticated-orcid":false,"given":"Kurt D.","family":"Hankenson","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3209-0026","authenticated-orcid":false,"given":"J. 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