Funding outcome

The Forkhead transcription factor FOXC1 plays an important role in development and disease. The disorders caused by FOXC1 mutation are extensive and the mechanisms by which alterations cause disorders as diverse as pediatric glaucoma, pediatric stroke, congenital heart disease, breast cancer, deafness and many others, remain unclear. The lab I am joining this summer has exciting evidence for a link between these seemingly different disorders: this link is an alteration to an essential cellular structure (the primary cilium), which functions as a satellite antenna for cells and controls the reception of signals that are essential for cellular and organ health. In addition, they have evidence that the spatial organization of cells, which are very precisely arranged in all tissues, is perturbed by FOXC1 mutation. Simplistically, each cell receives a GPS signal that ensures it is correctly orientated relative to its neighbours, and this signal is then propagated across the plane of a tissue. FOXC1 appears to influence this process and alter the precise position of the primary cilium, leading to impaired function in a range of organs. My role during the summer studentship will be to assess at least one additional tissue for changes to this process (polarity) and determine whether this replicates what has already been identified in the cornea. Potentially this research may confirm a common mechanism for multiple pediatric disorders and identify steps that could be targeted therapeutically