title: A ciliopathy with hydrocephalus, isolated craniosynostosis, hypertelorism, and clefting caused by deletion of Kif3a.
abstract: Malformations of the facial midline are a consistent feature among individuals with defects in primary cilia. Here, we provide a framework in which to consider how these primary cilia-dependent facial anomalies occur. We generated mice in which the intraflagellar transport protein Kif3a was deleted in cranial neural crest cells. The Kif3a phenotypes included isolated metopic craniosynostosis, delayed closure of the anterior fontanelles, and hydrocephalus, as well as midline facial anomalies including hypertelorism, cleft palate, and bifid nasal septum. Although all cranial neural crest cells had truncated primary cilia as a result of the conditional deletion, only those in the midline showed evidence of hyper-proliferation and ectopic Wnt responsiveness. Thus, cranial neural crest cells do not rely on primary cilia for their migration but once established in the facial prominences, midline cranial neural crest cells require Kif3a function in order to integrate and respond to Wnt signals from the surrounding epithelia.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA 94305, United States.
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA 94305, United States.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA 94305, United States; College of Medicine, University of Arizona, Tucson, AZ 85721, United States.
authors.forename: C
authors.initials: C
authors.lastname: Johnson
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA 94305, United States. Electronic address: jhelms@stanford.edu.
authors.forename: J A
authors.initials: JA
authors.lastname: Helms
mesh_terms: D000818:Animals; D002923:Cilia / Q000502:physiology*; D002972:Cleft Palate / Q000235:genetics*; D055762:Cranial Fontanelles / Q000002:abnormalities; D003398:Craniosynostoses / Q000235:genetics*; D006849:Hydrocephalus / Q000235:genetics*; D006972:Hypertelorism / Q000235:genetics*; D016547:Kinesins / Q000235:genetics*; D008822:Mice, Transgenic; D009154:Mutation; D009432:Neural Crest / Q000378:metabolism / Q000473:pathology; D054258:Neural Plate / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D060449:Wnt Signaling Pathway
chemical_list: C490202:Kif3a protein, mouse; D016547:Kinesins
keywords: Cranial neural crest; Craniofacial; Hedgehog; Intraflagellar transport protein; Midline; Syndrome; Wnt