Dissection of Celsr1/Flamingo function in vertebrate morphogenesis. (360G-Wellcome-095824_Z_11_Z)

Planar cell polarity (PCP) orchestrates the coordinated orientation of cell structures within the plane of a tissue. In Drosophila, the asymmetric sub-cellular distribution of PCP components defines the position and alignment of epithelial structures. How specific distribution of vertebrate PCP proteins impacts on their role(s) during the complex morphogenesis that shapes embryo development is less well understood. Celsr1/Flamingo is a PCP signalling component capable of homophilic interaction w hose bipolar distribution at lateral membranes directs E-cadherin and planar cell divisions along the mammalian anterior-posterior (A-P) axis. This proposal has three goals. Firstly, to determine whether the recently reported distribution of Celsr1 to the basal membrane of neuroepithelial cells is polarised along the A-P axis of the vertebrate hindbrain and directs the tangential migration of cranial neurons via interaction with known basal membrane adhesion components. Secondly, to determine wh ether vertebrate PCP proteins such as Scribble, a known apico-basal determinant in Drosophila, influence how Celsr1 protein becomes localised in different epithelia. Thirdly, to map the structures within Celsr1 which drive the differential localisation of specific Celsr1 proteins. These studies will elucidate the fundamental importance of differential Celsr1 protein distribution and how apico-basal and planar polarities intersect to organise vertebrate morphogenesis.