The coordinated polarisation of cells within an organism is essential for correct organ development. For example in the developing wing of the fruit fly, Drosophila, individual cells can sense the overall axes of the tissue in which they reside. Using these axes, the cells
undergo oriented cell divisions to ensure the final wing develops into the characteristic size and shape. Furthermore, each cell within the wing produces a single hair pointing along the wing axis. Loss of coordinated planar polarity results in characteristic swirling of these hairs.
A ‘core’ pathway of proteins are essential for correct polarisation. This system includes the transmembrane proteins Frizzled, Flamingo and Strabismus, as well as the cytoplasmic proteins
Dishevelled, Prickle and Diego. These core proteins localise
asymmetrically within epithelial cells, prior to any physical signs of
Two transmembrane proteins are found to be essential for
coordinating this behaviour, known as Fat (Ft) and Dachsous (Ds). Loss of either one of these molecules results in shorter, fatter wings.
Even though Ft and Ds are uniformly expressed across the
developing wing blade, they are modified by a further protein; a
golgi-localised kinase, known as Four-jointed (Fj). The graded
expression of this kinase appears to result in the asymmetric
localisation of Ft and Ds, with Ft enriched at proximal cell edges and Ds at distal junctions.
I am using a combination of experimental and computational
approaches to understand how gradients and boundaries of
expression can be converted into strong asymmetric localisation of target molecules. I am developing mathematical models, using
ordinary differential equations (ODEs), to describe these two
polarity systems. I am now interrogating my model under various
simulation conditions to investigate how planar polarity is
established and regulated.