{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T21:01:39Z","timestamp":1786914099368,"version":"build-2736575974"},"reference-count":65,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea\n              https:\/\/ror.org\/013aysd81","doi-asserted-by":"publisher","award":["RS-2024-00457696"],"award-info":[{"award-number":["RS-2024-00457696"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health & Welfare\n              https:\/\/ror.org\/00vxgjw72","award":["RS-2025-02223691"],"award-info":[{"award-number":["RS-2025-02223691"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tooth development or odontogenesis is a complex morphogenetic process that requires tightly regulated interactions between the oral epithelium and mesenchyme of neural crest origin. In this narrative review, we compile existing knowledge regarding gene regulatory networks and epigenetic factors throughout tooth development from initiation to eruption. Signaling between the epithelium and mesenchyme is mediated by four conserved pathways\u2014Wnt\/\u03b2-catenin, bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and Sonic hedgehog (Shh)\u2014which operate iteratively and interact through extensive crosstalk at each developmental stage. Transcription factors, such as PAX9, MSX1, PITX2, and LEF1, interpret these signals to control cell fate decisions and differentiation. Epigenetic modifications, including DNA methylation, histone modifications, and microRNA-mediated regulation, provide additional layers of control that fine-tune gene expression programs. Unlike existing reviews that address these regulatory mechanisms separately, here we integrate signaling pathways, transcription factor networks, epigenetic regulation, human genetic disorders, dental stem cell biology, and recent single-cell transcriptomic insights into a unified framework. We discuss opportunities to apply developmental biology knowledge towards regenerative dentistry goals, including iPSC-derived dental models and spatially resolved multi-omics approaches, while acknowledging the considerable gap between preclinical findings and clinical applications.<\/jats:p>","DOI":"10.3390\/cells15070618","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T15:20:47Z","timestamp":1774884047000},"page":"618","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrated Genetic Networks and Epigenetic Regulation inTooth Development and Maturation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6532-9729","authenticated-orcid":false,"given":"Dong-Joon","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Oral Histology, College of Dentistry, Dankook University, Cheonan 31116, Republic of Korea"},{"name":"Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3086-7823","authenticated-orcid":false,"given":"Hyung-Jin","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6935-0936","authenticated-orcid":false,"given":"Jeong-Oh","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1242\/jcs.00410","article-title":"Epithelial-mesenchymal signalling regulating tooth morphogenesis","volume":"116","author":"Thesleff","year":"2003","journal-title":"J. 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