{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:00Z","timestamp":1787028540892,"version":"build-2736575974"},"reference-count":33,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270949"],"award-info":[{"award-number":["82270949"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370916"],"award-info":[{"award-number":["82370916"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2023XDRHXMPT11"],"award-info":[{"award-number":["2023XDRHXMPT11"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yantai School\u2013City Integration Development Project\u2013Digital Stomatology Innovation Research platform","award":["82270949"],"award-info":[{"award-number":["82270949"]}]},{"name":"Yantai School\u2013City Integration Development Project\u2013Digital Stomatology Innovation Research platform","award":["82370916"],"award-info":[{"award-number":["82370916"]}]},{"name":"Yantai School\u2013City Integration Development Project\u2013Digital Stomatology Innovation Research platform","award":["2023XDRHXMPT11"],"award-info":[{"award-number":["2023XDRHXMPT11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Putatively, tooth agenesis was attributed to the initiation failure of tooth germs, though little is known about the histological and molecular alterations. To address if constitutively active FGF signaling is associated with tooth agenesis, we activated Fgf8 in dental mesenchyme with Osr-cre knock-in allele in mice (Osr2-creKI; Rosa26R-Fgf8) and found incisor agenesis and molar microdontia. The cell survival assay showed tremendous apoptosis in both the Osr2-creKI; Rosa26R-Fgf8 incisor epithelium and mesenchyme, which initiated incisor regression from cap stage. In situ hybridization displayed vanished Shh transcription, and immunostaining exhibited reduced Runx2 expression and enlarged mesenchymal Lef1 domain in Osr2-creKI; Rosa26R-Fgf8 incisors, both of which were suggested to enhance apoptosis. In contrast, Osr2-creKI; Rosa26R-Fgf8 molar germs displayed mildly suppressed Shh transcription, and the increased expression of Ectodin, Runx2 and Lef1. Although mildly smaller than WT controls prenatally, the Osr2-creKI; Rosa26R-Fgf8 molar germs produced a miniature tooth with impaired mineralization after a 6-week sub-renal culture. Intriguingly, the implanted Osr2-creKI; Rosa26R-Fgf8 molar germs exhibited delayed odontoblast differentiation and accelerated ameloblast maturation. Collectively, the ectopically activated Fgf8 in dental mesenchyme caused incisor agenesis by triggering incisor regression and postnatal molar microdontia. Our findings reported tooth agenesis resulting from the regression from the early bell stage and implicated a correlation between tooth agenesis and microdontia.<\/jats:p>","DOI":"10.3390\/ijms25137045","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T11:19:02Z","timestamp":1719487142000},"page":"7045","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ectopic Activation of Fgf8 in Dental Mesenchyme Causes Incisor Agenesis and Molar Microdontia"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7807-2519","authenticated-orcid":false,"given":"Yu","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Stomatology, Binzhou Medical University, Yantai 264003, China"},{"name":"Department of Oral Pathology, School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3584-0224","authenticated-orcid":false,"given":"Chao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"dev184754","DOI":"10.1242\/dev.184754","article-title":"Molecular and cellular mechanisms of tooth development, homeostasis and repair","volume":"147","author":"Yu","year":"2020","journal-title":"Development"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/j.1469-7580.2011.01352.x","article-title":"Expression of fibroblast growth factors (Fgfs) in murine tooth development","volume":"218","author":"Porntaveetus","year":"2011","journal-title":"J. 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