Abstract for presentation at 11th International Congress of Human Genetics

Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates

  • Dr Alison Ross, Institute of Child Health, University College London, United Kingdom
  • Miss Helen May-Simera, Institute of Child Health, University College London, United Kingdom
  • Dr Masatake Kai, Dept of Anatomy and Developmental Biology, University College London, United Kingdom
  • Dr Josephine Hill, Institute of Child Health, University College London, United Kingdom
  • Dr Masazumi Tada, Dept of Anatomy and Developmental Biology, University College London, United Kingdom
  • Dr Nicholas Katsanis, Institute of Genetic Medicine, Johns Hopkins University, Baltimore, United States
  • Prof Andrew Forge, Centre for Auditory Research, The Ear Institute, University College London, United Kingdom
  • Prof Philip Beales, Institute of Child Health, University College London, United Kingdom

    • The evolutionarily-conserved planar cell polarity (PCP) pathway (or non-canonical Wnt pathway) drives several important cellular processes, including epithelial cell polarization, cell migration, and mitotic spindle orientation. In vertebrates, PCP genes play a vital role in polarized convergent extension (CE) movements during gastrulation and neurulation. Here, we show that mice with mutations in genes involved in Bardet-Biedl syndrome (BBS), a disorder associated with ciliary dysfunction, share phenotypes with PCP mutants including open eyelids, neural tube defects and disrupted cochlear stereociliary bundles. Furthermore, we demonstrate genetic interactions between BBS genes and a PCP gene, Vangl2, in both mouse and zebrafish; in the latter we show that the augmented phenotype results from enhanced defective CE movements. We also show that Vangl2 localizes to the basal body and axoneme of ciliated cells, a pattern reminiscent of the BBS proteins. These data suggest, for the first time, that cilia are intrinsically involved in PCP processes.

    Conference Organiser - ICMS Pty Ltd