Alexander Fletcher: Planar polarity in epithelial morphogenesis

Polarisation is one of the most basic levels of cell organisation. In developing epithelial tissues, sheets of cells become planar polarised – within the plane of the tissue – which is vital for coordinated cell behaviours during morphogenesis. Half a century ago, transplantation experiments revealed the ability of cells to communicate their planar polarity with their neighbours, but the underlying mechanisms remain controversial. Here, we combine mathematical modelling with re-examination of non-autonomous clone phenotypes in the Drosophila wing to characterise mechanisms by which polarity information may flow bidirectionally between the polarity proteins Frizzled (Fz) and Van Gogh (Vang). Unexpectedly, our modelling suggests that local intracellular feedback interactions confer directionality of information flow indirectly as a consequence of protein sorting. We conclude that directional signalling between cells depends on (i) the ability of polarity proteins to preferentially form asymmetric intercellular complexes, and (ii) the balance of feedback interactions between components of these complexes. In particular, the observed bidirectionality of signalling can be reproduced in our models through more than one combination of molecular wirings, suggesting avenues for future experimental investigations. We conclude by discussing ongoing work on the integration of planar polarity and tissue mechanics in epithelial morphogenesis.