{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:48:01Z","timestamp":1790837281374,"version":"4.1.0"},"reference-count":54,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":1598,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"funder":[{"DOI":"10.13039\/501100001279","name":"Great Ormond Street Hospital Charity","doi-asserted-by":"publisher","award":["W0908"],"award-info":[{"award-number":["W0908"]}],"id":[{"id":"10.13039\/501100001279","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Syndromic craniosynostosis caused by mutations in FGFR2 is characterised by developmental pathology in both endochondral and membranous skeletogenesis. Detailed phenotypic characterisation of features in the membranous calvarium, the endochondral cranial base and other structures in the axial and appendicular skeleton has not been performed at embryonic stages. We investigated bone development in the Crouzon mouse model (Fgfr2C342Y) at pre- and post-ossification stages to improve understanding of the underlying pathogenesis.<\/jats:p><jats:p>Phenotypic analysis was performed by whole mount skeletal staining (Alcian Blue\/Alizarin Red) and histological staining of sections of CD1 wild-type (WT), Fgfr2C342Y\/+ heterozygous (HET) and Fgfr2C342Y\/C342Y homozygous (HOM) mouse embryos from E12.5-E17.5 stages. Gene expression (Sox9, Shh, Fgf10, and Runx2) was studied by in situ hybridisation and protein expression (COL2A1) by immunohistochemistry.<\/jats:p><jats:p>Our analysis has identified severely decreased osteogenesis in parts of the craniofacial skeleton together with increased chondrogenesis in parts of the endochondral and cartilaginous skeleton in HOM embryos. The Sox9 expression domain in tracheal and basi-cranial chondrocytic precursors at E13.5 in HOM embryos is increased and expanded, correlating with the phenotypic observations which suggests FGFR2 signalling regulates Sox9 expression. Combined with abnormal staining of type II collagen in pre-chondrocytic mesenchyme, this is indicative of a mesenchymal condensation defect.<\/jats:p><jats:p>An expanded spectrum of phenotypic features observed in the Fgfr2C342Y\/C342Y mouse embryo paves the way towards better understanding the clinical attributes of human Crouzon-Pfeiffer syndrome. FGFR2 mutation results in impaired skeletogenesis, however our findings suggest that many phenotypic aberrations stem from a primary failure of pre-chondrogenic\/osteogenic mesenchymal condensation and links FGFR2 to SOX9, a principal regulator of skeletogenesis.<\/jats:p>","DOI":"10.1242\/bio.022178","type":"journal-article","created":{"date-parts":[[2017,1,10]],"date-time":"2017-01-10T01:25:22Z","timestamp":1484011522000},"source":"Crossref","is-referenced-by-count":22,"title":["Analysis of the Fgfr2C342Y mouse model shows condensation defects due to misregulation of Sox9 expression in prechondrocytic mesenchyme"],"prefix":"10.1242","author":[{"given":"Emma","family":"Peskett","sequence":"first","affiliation":[{"name":"UCL Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samin","family":"Kumar","sequence":"additional","affiliation":[{"name":"UCL Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Baird","sequence":"additional","affiliation":[{"name":"UCL Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janhvi","family":"Jaiswal","sequence":"additional","affiliation":[{"name":"UCL Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Li","sequence":"additional","affiliation":[{"name":"UCL Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanca","family":"Patel","sequence":"additional","affiliation":[{"name":"UCL Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Britto","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital Craniofacial Unit, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1751-0317","authenticated-orcid":false,"given":"Erwin","family":"Pauws","sequence":"additional","affiliation":[{"name":"UCL Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2017,1,1]]},"reference":[{"key":"2021042423493780100_BIO022178C1","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1016\/j.ijporl.2014.09.019","article-title":"Hearing loss in syndromic craniosynostoses: otologic manifestations and clinical findings","volume":"78","author":"Agochukwu","year":"2014","journal-title":"Int. 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