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Altered activity of the Wnt/b-catenin and BMP pathways mimics skeletal phenotypes of cerebro-costo-mandibular syndrome in chick embryos

Research output: Contribution to conferenceAbstract

Original languageEnglish
DatePublished - 9 Aug 2019
Event19th Congress of the International Federation of Associations of Anatomists - Excel Exhibition Centre, London, United Kingdom
Duration: 9 Aug 201911 Aug 2019


Conference19th Congress of the International Federation of Associations of Anatomists
CountryUnited Kingdom
Internet address


Although the spliceosome is required for the transcription of most of the genes in our body, the phenotype of spliceosomal defect syndromes is largely limited to specific tissues such as the bones, retina, brain and motor neurons, depending on the affected spliceosomal component. Cerebro-Costo-Mandibular syndrome (CCMS) is an example of one of these spliceosomal syndromes, a congenital skeletal disorder caused by mutation of SNRPB, encoding Small nuclear ribonucleoprotein polypeptide B/B’. CCMS is characterised by discontinuity of ribs, called rib-gaps, at the posterior part of the shaft, along with scoliosis and craniofacial defects such as micrognathia, glossoptosis and cleft palate. We have found that SNRPB knock-down affects the Wnt/-catenin pathway while increasing cells’ sensitivity to BMP signals. These pathways are important in many aspects of development, including formation of pharyngeal arches which give rise to the maxilla, mandible and tongue, patterning of somites where the axial skeleton originates, and differentiation of cartilages and bones. Local modification of these pathways in somites in vivo recapitulated the posterior rib-gap phenotype in the costal cartilage in model animal embryos. In vitro, knock-down of SNRPB in osteoblast-like cells SaOS-2 attenuated upregulation of Runx2, ALP and Osterix that are required for osteogenesis. It was also found in SaOS-2 cells that Dlx5, a gene that crucially initiates and maintains Runx2 expression for osteogenesis, was alternatively spliced to form a non-functional, truncated version. These results suggest that altered activities of Wnt/-catenin and BMP pathways as well as splicing defects of specific genes contribute to the phenotype in CCMS.


19th Congress of the International Federation of Associations of Anatomists

Duration9 Aug 201911 Aug 2019
Location of eventExcel Exhibition Centre
CountryUnited Kingdom
Web address (URL)
Degree of recognitionInternational event

Event: Conference


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