title: Morphological comparison of the craniofacial phenotypes of mouse models expressing the Apert FGFR2 S252W mutation in neural crest- or mesoderm-derived tissues.
abstract: Bones of the craniofacial skeleton are derived from two distinct cell lineages, cranial neural crest and mesoderm, and articulate at sutures and synchondroses which represent major bone growth sites. Premature fusion of cranial suture(s) is associated with craniofacial dysmorphogenesis caused in part by alteration in the growth potential at sutures and can occur as an isolated birth defect or as part of a syndrome, such as Apert syndrome. Conditional expression of the Apert FGFR2 S252W mutation in cells derived from mesoderm was previously shown to be necessary and sufficient to cause coronal craniosynostosis. Here we used micro computed tomography images of mice expressing the Apert mutation constitutively in either mesoderm- or neural crest-derived cells to quantify craniofacial shape variation and suture fusion patterns, and to identify shape changes in craniofacial bones derived from the lineage not expressing the mutation, referred to here as secondary shape changes. Our results show that at postnatal day 0: (i) conditional expression of the FGFR2 S252W mutation in neural crest-derived tissues causes a more severe craniofacial phenotype than when expressed in mesoderm-derived tissues; and (ii) both mesoderm- and neural crest-specific mouse models display secondary shape changes. We also show that premature suture fusion is not necessarily dependent on the expression of the FGFR2 S252W mutation in the sutural mesenchyme. More specifically, it appears that suture fusion patterns in both mouse models are suture-specific resulting from a complex combination of the influence of primary abnormalities of biogenesis or signaling within the sutures, and timing.
authors.affiliation: Department of Anthropology, Pennsylvania State University, University Park, PA, USA.
authors.forename: Yann
authors.initials: Y
authors.lastname: Heuzé
authors.affiliation: Department of Anthropology, Pennsylvania State University, University Park, PA, USA.
authors.forename: Nandini
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, NY, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Basilico
authors.affiliation: Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Ethylin Wang
authors.initials: EW
authors.lastname: Jabs
authors.affiliation: Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Holmes
authors.affiliation: Department of Anthropology, Pennsylvania State University, University Park, PA, USA. Electronic address: jtr505@gmail.com.
authors.forename: Joan T
authors.initials: JT
authors.lastname: Richtsmeier
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005147:Facial Bones / Q000196:embryology; D008648:Mesoderm / Q000196:embryology*; D051379:Mice; D009154:Mutation; D009432:Neural Crest / Q000196:embryology*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D012886:Skull / Q000196:embryology
chemical_list: C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: Apert syndrome; Craniosynostosis; FGFR2; Mesoderm; Neural crest; Suture fusion pattern