Journal article
Bardet-Biedl syndrome 3 regulates the development of cranial base midline structures
Bone (New York, N.Y.), Vol.101, pp.179-190
08/2017
DOI: 10.1016/j.bone.2016.02.017
PMCID: PMC5519131
PMID: 27170093
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.
•Craniofacial dysmorphology in BBS3 deficient mice was characterized here.•Mid-sagittal regions of the cranial base were hypomorphic in Bbs3−/− embryos, with fewer cells.•Pathogenic involvement of the impaired migration of Bbs3−/− cells toward cranial midline was suggested.•These findings contribute to the better understandings and treatment of craniofacial symptoms of BBS.
Details
- Title: Subtitle
- Bardet-Biedl syndrome 3 regulates the development of cranial base midline structures
- Creators
- Makiri Kawasaki - Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, JapanYayoi Izu - Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, JapanTadayoshi Hayata - Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, JapanHisashi Ideno - Department of Pharmacology, Tsurumi University School of Dental Medicine, JapanAkira Nifuji - Department of Pharmacology, Tsurumi University School of Dental Medicine, JapanVal C Sheffield - Department of Pediatrics, University of Iowa College of Medicine, United StatesYoichi Ezura - Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, JapanMasaki Noda - Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan
- Resource Type
- Journal article
- Publication Details
- Bone (New York, N.Y.), Vol.101, pp.179-190
- DOI
- 10.1016/j.bone.2016.02.017
- PMID
- 27170093
- PMCID
- PMC5519131
- NLM abbreviation
- Bone
- ISSN
- 8756-3282
- eISSN
- 1873-2763
- Publisher
- Elsevier Inc
- Grant note
- name: Grant-in-Aid for JSPS Fellows, award: 13J09828; name: Grant-in-Aid for Scientific Research, award: 26253085, 16K15655; DOI: 10.13039/100011313, name: TBRF; name: Abnormal Metabolism Research Foundation
- Language
- English
- Date published
- 08/2017
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984065485102771
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