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Malformation of the cranial base in humans leads CFAs, such as midfacial hypoplasia and craniosynostosis. These patients have significant burdens associated with breathing, speaking, and chewing. Invasive surgical intervention is the current primary option to correct these structural deficiencies. Understanding molecular cellular mechanism for craniofacial development would provide novel therapeutic options for CFAs. In this study, we found that enhanced bone morphogenetic protein (BMP) signaling in cranial neural crest cells (NCCs) (<jats:italic>P0\u2010Cre;caBmpr1a<\/jats:italic> mice) causes premature fusion of intersphenoid synchondrosis (ISS) resulting in leading to short snouts and hypertelorism. Histological analyses revealed reduction of proliferation and higher cell death in ISS at postnatal day 3. We demonstrated to prevent the premature fusion of ISS in <jats:italic>P0\u2010Cre;caBmpr1a<\/jats:italic> mice by injecting a p53 inhibitor Pifithrin\u2010\u03b1 to the pregnant mother from E15.5 to E18.5, resulting in rescue from short snouts and hypertelorism. We further demonstrated to prevent premature fusion of cranial sutures in <jats:italic>P0\u2010Cre;caBmpr1a<\/jats:italic> mice by injecting Pifithrin\u2010\u03b1 through E8.5 to E18.5. These results suggested that enhanced BMP\u2010p53\u2010induced cell death in cranial NCCs causes premature fusion of ISS and sutures in time\u2010dependent manner.<\/jats:p>","DOI":"10.1002\/dvg.23509","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T16:38:25Z","timestamp":1673282305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Augmentation of bone morphogenetic protein signaling in cranial neural crest cells in mice deforms skull base due to premature fusion of intersphenoidal synchondrosis"],"prefix":"10.1002","volume":"61","author":[{"given":"Hiroki","family":"Ueharu","sequence":"first","affiliation":[{"name":"Department of Biologic and Materials Sciences School of Dentistry, University Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haichun","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences School of Dentistry, University Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Hayano","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Okayama University Hospital  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Zapien\u2010Guerra","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences School of Dentistry, University Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences School of Dentistry, University Michigan  Ann Arbor Michigan USA"},{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) and Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of Stomatology, Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6268-4204","authenticated-orcid":false,"given":"Yuji","family":"Mishina","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences School of Dentistry, University Michigan  Ann Arbor Michigan 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