title: Frontal Bone Insufficiency in Gsk3β Mutant Mice.
abstract: The development of the mammalian skull is a complex process that requires multiple tissue interactions and a balance of growth and differentiation. Disrupting this balance can lead to changes in the shape and size of skull bones, which can have serious clinical implications. For example, insufficient ossification of the bony elements leads to enlarged anterior fontanelles and reduced mechanical protection of the brain. In this report, we find that loss of Gsk3β leads to a fully penetrant reduction of frontal bone size and subsequent enlarged frontal fontanelle. In the absence of Gsk3β the frontal bone primordium undergoes increased cell death and reduced proliferation with a concomitant increase in Fgfr2-IIIc and Twist1 expression. This leads to a smaller condensation and premature differentiation. This phenotype appears to be Wnt-independent and is not rescued by decreasing the genetic dose of β-catenin/Ctnnb1. Taken together, our work defines a novel role for Gsk3β in skull development.
authors.affiliation: Craniofacial Development and Stem Cell Biology, Floor 27, Tower Wing, Guy's Campus, King's College London, London, United Kingdom SE1 9RT.
authors.forename: Heather
authors.initials: H
authors.lastname: Szabo-Rogers
authors.affiliation: Craniofacial Development and Stem Cell Biology, Floor 27, Tower Wing, Guy's Campus, King's College London, London, United Kingdom SE1 9RT.
authors.forename: Wardati
authors.initials: W
authors.lastname: Yakob
authors.affiliation: Craniofacial Development and Stem Cell Biology, Floor 27, Tower Wing, Guy's Campus, King's College London, London, United Kingdom SE1 9RT.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D019465:Craniofacial Abnormalities / Q000201:enzymology / Q000473:pathology; D004622:Embryo, Mammalian / Q000473:pathology; D005624:Frontal Bone / Q000196:embryology / Q000201:enzymology* / Q000473:pathology*; D017353:Gene Deletion; D038362:Glycogen Synthase Kinase 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008817:Mice, Mutant Strains; D009432:Neural Crest / Q000166:cytology; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D051153:Wnt Proteins; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3