title: Multiple postnatal craniofacial anomalies are characterized by conditional loss of polycystic kidney disease 2 (Pkd2).
abstract: Polycystin 2 (Pkd2), which belongs to the transient receptor potential family, plays a critical role in development. Pkd2 is mainly localized in the primary cilia, which also function as mechanoreceptors in many cells that influence multiple biological processes including Ca(2+) influx, chemical activity and signalling pathways. Mutations in many cilia proteins result in craniofacial abnormalities. Orofacial tissues constantly receive mechanical forces and are known to develop and grow through intricate signalling pathways. Here we investigate the role of Pkd2, whose role remains unclear in craniofacial development and growth. In order to determine the role of Pkd2 in craniofacial development, we located expression in craniofacial tissues and analysed mice with conditional deletion of Pkd2 in neural crest-derived cells, using Wnt1Cre mice. Pkd2 mutants showed many signs of mechanical trauma such as fractured molar roots, distorted incisors, alveolar bone loss and compressed temporomandibular joints, in addition to abnormal skull shapes. Significantly, mutants showed no indication of any of these phenotypes at embryonic stages when heads perceive no significant mechanical stress in utero. The results suggest that Pkd2 is likely to play a critical role in craniofacial growth as a mechanoreceptor. Pkd2 is also identified as one of the genes responsible for autosomal dominant polycystic kidney disease (ADPKD). Since facial anomalies have never been identified in ADPKD patients, we carried out three-dimensional photography of patient faces and analysed these using dense surface modelling. This analysis revealed specific characteristics of ADPKD patient faces, some of which correlated with those of the mutant mice.
authors: Department of Craniofacial Development and Stem Cell Research, and Comprehensive Biomedical Research Centre, Dental Institute, King’s College London, London, UK.
authors: Roman H
authors: RH
authors: Khonsari
authors: Atsushi
authors: A
authors: Ohazama
authors: Ramin
authors: R
authors: Raouf
authors: Maiko
authors: M
authors: Kawasaki
authors: Katsushige
authors: K
authors: Kawasaki
authors: Thantrira
authors: T
authors: Porntaveetus
authors: Sarah
authors: S
authors: Ghafoor
authors: Peter
authors: P
authors: Hammond
authors: Michael
authors: M
authors: Suttie
authors: Guillaume A
authors: GA
authors: Odri
authors: Richard N
authors: RN
authors: Sandford
authors: John N
authors: JN
authors: Wood
authors: Paul T
authors: PT
authors: Sharpe
mesh_terms: D000328:Adult; D000818:Animals; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology; D005145:Face; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008465:Mechanoreceptors / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D050396:TRPP Cation Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D050396:TRPP Cation Channels