{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:29:30Z","timestamp":1784543370497,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>The pivotal role of FGF18 in the regulation of craniofacial and skeletal development has been well established. Previous studies have demonstrated that mice with deficiency in <jats:italic>Fgf18<\/jats:italic> exhibit severe craniofacial dysplasia. Recent clinical reports have revealed that the duplication of chromosome 5q32-35.3, which encompasses the <jats:italic>Fgf18<\/jats:italic> gene, can lead to cranial bone dysplasia and congenital craniosynostosis, implicating the consequence of possible overdosed FGF18 signaling. This study aimed to test the effects of augmented FGF18 signaling by specifically overexpressing the <jats:italic>Fgf18<\/jats:italic> gene in cranial neural crest cells using the <jats:italic>Wnt1-Cre;pMes-Fgf18<\/jats:italic> mouse model. The results showed that overexpression of <jats:italic>Fgf18<\/jats:italic> leads to craniofacial abnormalities in mice similar to the Pierre Robin sequence in humans, including abnormal tongue morphology, micrognathia, and cleft palate. Further examination revealed that elevated levels of <jats:italic>Fgf18<\/jats:italic> activated the Akt and Erk signaling pathways, leading to an increase in the proliferation level of tongue tendon cells and alterations in the contraction pattern of the genioglossus muscle. Additionally, we observed that excessive FGF18 signaling contributed to the reduction in the length of Meckel\u2019s cartilage and disrupted the development of condylar cartilage, ultimately resulting in mandibular defects. These anomalies involve changes in several downstream signals, including Runx2, p21, Akt, Erk, p38, Wnt, and Ihh. This study highlights the crucial role of maintaining the balance of endogenous FGF18 signaling for proper craniofacial development and offers insights into potential formation mechanisms of the Pierre Robin sequence.<\/jats:p>","DOI":"10.3389\/fcell.2024.1376814","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T04:43:19Z","timestamp":1713328999000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Overexpression of Fgf18 in cranial neural crest cells recapitulates Pierre Robin sequence in mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Yi","family":"Lv","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chensheng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanding","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1093\/hmg\/ddw153","article-title":"Meckel's and condylar cartilages anomalies in achondroplasia result in defective development and growth of the mandible","volume":"25","author":"Biosse Duplan","year":"2016","journal-title":"Hum. 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