Planar polarity as a model for understanding self-organisation from molecular to tissue scales

A fundamental objective of developmental biology is to understand self-organised patterning, whereby individual molecular interactions at the nanometre scale contribute to tissue patterning beyond the millimetre scale. Significant challenges in achieving this are following the localisation and interactions of individual molecules in living tissues, and showing the sufficiency of particular interactions to drive tissue patterning. We study a simple in vivo model: the ability of cells in the Drosophila wing epithelium to self-organise to coordinate their polarity with their neighbours (‘planar polarity’). Decades of research have identified key proteins, but how their molecular interactions lead to planar polarity remains unresolved. To move forward, we will exploit multicolour single molecule microscopy and precise spatiotemporal manipulation of gene function in the developing wing. In parallel, we will reconstruct molecular behaviours in heterologous cell culture. We will investigate processes occurring at different size scales, that when integrated lead to tissue planar polarisation. Specifically, how: (1) planar polarity proteins mediate molecular symmetry breaking at the nanometre scale by assembling into asymmetric intercellular complexes (2) local protein sorting mechanisms organise protein complexes into polarised domains tens of nanometres in size (3) cellular self-organisation mechanisms segregate protein complexes to opposite cell edges at the micrometre scale