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Functional charaterization of Vangl2 interactions


Planar cell polarity (PCP) genes were originally identified in invertebrates (Drosophila Melanogaster) for their role in the uniform orientation of a cell or a group of cells within the plane of the epithelium. During the last five years, numerous studies have shown that vertebrate, but more importantly mammalian homologues of some of these genes are involved in various developmental processes.

More importantly, the disruption of these processes leads to diverse pathologies such as neural tube defects, polycystic kidney disease, inner ear dysfunctions (hearing, balance) or Bardet Biedl syndrome. These developmental processes rely on a set of genes whose PCP function is conserved in mammals and Drosophila Melanogaster for some, or only present in mammals for others. We have identified Scrb1 and Vangl2 as two essential genes for the PCP in mammals, and have recently demonstrated that the two proteins belong to a common signalling pathway in vitro and in vivo.

We also showed, with another group, that some of the very upstream mechanisms of the PCP pathway seem different from invertebrates. In fact, the exact nature of the intracellular components participating in the intracellular cascade leading to the establishment of PCP is virtually unknown in mammals. It is now important to identify not only genes involved in PCP in mammals, but also the intracellular signalling cascades leading to the establishment of that PCP.

Our project will use a multidisciplinary approach, combining biochemistry to further identify binding partners for Vangl2 and Scrb1, and genetics, cell biology and imaging procedures to characterize these interactions at the functional level. We hope that this project, in the long term, will give a much better understanding of the signalling pathway centred on the Vangl2-Scrb1 module in mammals.

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