Specification and patterning of the Drosophila retina by the Pax6 transcription factor

Project Summary: A critical step during development is organogenesis, the process by which primordial tissues give rise to complex three-dimensional organs. The question of how individual organs acquire their unique identity is of fundamental importance to understanding both normal development and congenital disease. The over-arching goal of this project is to understand how the earliest steps in the process of eye formation are controlled. Our efforts will focus specifically on the role that the Pax6 transcription factors, Eyeless (Ey) and Twin of Eyeless (Toy), play in specifying and patterning the Drosophila compound eye. The fly retina is an excellent model system for studying organ formation because the steps of its cellular development are well defined, a robust collection of genetic tools allow for the manipulation of relevant genes, a wealth of markers allow for identifying deviations in developmental trajectories, and the tissue is amenable to genomic methods which illuminate the transcriptome, transcription factor binding, chromatin accessibility, and histone modifications. While an abundance of reagents and tools has been applied to the study of other genes involved in eye formation, understanding the roles that Ey and Toy has been hampered by a scarcity of molecular and genetic reagents associated with these genes. Another obstacle has been the near complete lack of attention placed on studying the role that Toy plays in the eye. As such, we have an incomplete view of Pax6 function which is skewed heavily towards Ey. We have overcome these limitations by creating new methods as well as new molecular and genetic reagents that will allow us to determine the individual and combined contributions that Ey and Toy make to eye formation and patterning. Our studies will, therefore, fill an enormous gap in our knowledge about these important transcription factors. 1Our studies will also impact human health as mutations in human Pax6 are the most common single cause of Aniridia, a congenital eye disorder that occurs 1 in 50,000 live births. Patients with this disorder suffer from reductions in visual acuity, increased sensitivity to light, and progressive loss in vision.