Project details

Congenital eye malformations account for a quarter of all childhood blindness, directly impacting an individual’s capacity for personal development with lifelong consequences. Often associated with broader genetic syndromes, the best known cause is mutations in genes that determine ocular anatomy in the early embryo. However many cases are never explained as the mutations occur in unknown genes, demonstrating the need to better understand the molecular processes regulating eye formation and malformation.

Embryonic eye development is robustly coordinated by a network of cell signalling interactions which handle communications between the different ocular tissues. Consequently, any deficiencies in this signalling infrastructure greatly compromise the emerging anatomy. Recent advances have identified many of the important signals while hinting at complex interactions which may bind them together in a pan-ocular network. This network appears to act repeatedly in the embryo to specify multiple ocular tissues and the outstanding challenge is to determine how different ocular cell types integrate these recurring signals at the molecular level.

The proposed research will meet this challenge by determining to what extent this network is re-used during eye development and by characterising the molecular interactions which bind the network together. Ocular signalling events will be systematically mapped against the developing anatomy to reveal likely signal interactions. Embryological methods will then be used to determine which signals interact and how those interactions define the emerging anatomy. Finally, a reverse gene replacement strategy will define exactly how those signals interact at a molecular level and reveal genetic mutations which may compromise eye formation.

It is hoped that this work will greatly assist the identification of candidate disease genes which may be screened for mutations in patients with congenital eye malformations. Successful identification of disease genes will contribute towards effective genetic counselling for patients and their families.