Molecular genetics of planar polarity in Drosophila (360G-Wellcome-078889_Z_05_Z)

Planar cell polarity (PCP) is exemplified by the direction of ciliary beat, the orientation of hairs or the alignment of stereocilia. The problem is pervasive and long range (how does information set up over an entire developing field convey axial information to single cells?) and local (how does a single cell read this polarising information and how does it liaise with its neighbours?). We have worked on PCP for 9 years using the Drosophila abdomen. We and others have shown that PCP depends on a novel mechanism. The pervasive system relies on interacting cadherin molecules (Dachsous, Fat) and the local system depends on the Frizzled receptor and another cadherin, Flamingo. We have published evidence that each cell is polarised by comparing the levels of activity of Frizzled in its neighbours, using the intercellular bridge made by Flamingo to do so. Now we want to test this model at the molecular level, using constructs made with all three cadherins and with Fz, assaying them both in flies and in cell culture. We will also investigate the long range system, asking how it receives information from the organising morphogen (Hedgehog) upstream and passes information to the local system downstream