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Signaling pathway networks and mechanotransduction are important factors to guide the lineage commitment of stem\/progenitor cells during craniofacial tissue morphogenesis. Here, we used tooth root development as a model to explore the roles of FGF signaling and mechanotransduction as well as their interaction in regulating the progenitor cell fate decision. We show that\n                    <jats:italic>Fgfr1<\/jats:italic>\n                    is expressed in the mesenchymal progenitor cells and their progeny during tooth root development. Loss of\n                    <jats:italic>Fgfr1<\/jats:italic>\n                    in\n                    <jats:italic>Gli1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+<\/jats:italic>\n                    <\/jats:sup>\n                    progenitors leads to hyperproliferation and differentiation, which causes narrowed periodontal ligament (PDL) space with abnormal cementum\/bone formation leading to ankylosis. We further show that aberrant activation of WNT signaling and mechanosensitive channel\n                    <jats:italic>Piezo2<\/jats:italic>\n                    occurs after loss of FGF signaling in\n                    <jats:italic>Gli1-Cre<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>ER<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>;Fgfr1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>fl\/fl<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Overexpression of\n                    <jats:italic>Piezo2<\/jats:italic>\n                    leads to increased osteoblastic differentiation and decreased\n                    <jats:italic>Piezo2<\/jats:italic>\n                    leads to downregulation of WNT signaling. Mechanistically, an FGF\/PIEZO2\/WNT signaling cascade plays a crucial role in modulating the fate of progenitors during root morphogenesis. Downregulation of WNT signaling rescues tooth ankylosis in\n                    <jats:italic>Fgfr1<\/jats:italic>\n                    mutant mice. Collectively, our findings uncover the mechanism by which FGF signaling regulates the fate decisions of stem\/progenitor cells, and the interactions among signaling pathways and mechanotransduction during tooth root development, providing insights for future tooth root regeneration.\n                  <\/jats:p>","DOI":"10.1038\/s41413-024-00345-5","type":"journal-article","created":{"date-parts":[[2024,6,23]],"date-time":"2024-06-23T23:10:29Z","timestamp":1719184229000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["FGF signaling modulates mechanotransduction\/WNT signaling in progenitors during tooth root development"],"prefix":"10.1038","volume":"12","author":[{"given":"Fei","family":"Pei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingwei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjun","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thach-Vu","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2477-7247","authenticated-orcid":false,"given":"Yang","family":"Chai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,24]]},"reference":[{"key":"345_CR1","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1038\/nature04957","volume":"441","author":"DT Scadden","year":"2006","unstructured":"Scadden, D. 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