title: Bardet-Biedl syndrome 3 regulates the development of cranial base midline structures.
abstract: Bardet-Biedl Syndrome (BBS) is an autosomal recessive disorder and is classified as one of the ciliopathy. The patients manifest a characteristic craniofacial dysmorphology but the effects of Bbs3 deficiency in the developmental process during the craniofacial pathogenesis are still incompletely understood. Here, we analyzed a cranial development of a BBS model Bbs3-/-mouse. It was previously reported that these mutant mice exhibit a dome-shape cranium. We show that Bbs3-/-mouse embryos present mid-facial hypoplasia and solitary central upper incisor. Morphologically, these mutant mice show synchondrosis of the cranial base midline due to the failure to fuse in association with loss of intrasphenoidal synchondrosis. The cranial base was laterally expanded and longitudinally shortened. In the developing cartilaginous primordium of cranial base, cells present in the midline were less in Bbs3-/-embryos. Expression of BBS3 was observed specifically in a cell population lying between condensed ectomesenchyme in the midline and the ventral midbrain at this stage. Finally, siRNA-based knockdown of Bbs3 in ATDC5 cells impaired migration in culture. Our data suggest that BBS3 is required for the development of cranial base via regulation of cell migration toward the midline where they promote the condensation of ectomesenchyme and form the future cartilaginous templates of cranial base.
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
authors.forename: Makiri
authors.initials: M
authors.lastname: Kawasaki
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Izu
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Hayata
authors.affiliation: Department of Pharmacology, Tsurumi University School of Dental Medicine, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ideno
authors.affiliation: Department of Pharmacology, Tsurumi University School of Dental Medicine, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nifuji
authors.affiliation: Department of Pediatrics, University of Iowa College of Medicine, United States.
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ezura
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan; Department of Orthopedics, Tokyo Medical and Dental University, Japan; Yokohama City Minato Red Cross Hospital, Japan. Electronic address: noda.mph@mri.tmd.ac.jp.
authors.forename: Masaki
authors.initials: M
authors.lastname: Noda
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D019291:Skull Base / Q000254:growth & development* / Q000378:metabolism*; D055114:X-Ray Microtomography; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029961:Zebrafish Proteins; D020727:ADP-Ribosylation Factors
keywords: Bardet-Biedl Syndrome; Cell migration; Craniofacial development; Primary cilia; Sonic Hedgehog (SHH)