View Program - 63rd Annual Drosophila Research Conference

The transcription factor PAX6 is the master regulator of eye development in all seeing animals. In Drosophila melanogaster, its orthologs Eyeless (Ey) and Twin of Eyeless (Toy) sit atop the retinal determination network (Rdn), which represents a group of around fourteen transcription factors and co-factors responsible for retinal specification and patterning. Many of PAX6’roles were first elucidated in Drosophila through studies of ey, and it’s been believed that the specific loss of ey would result in the collapse of the Rdn and the loss of eye development; while the early embryonic loss of toy results in a headless fly (both Ey and Toy are required for overall growth of the eye-antennal imaginal disc), toy knockdown during larval development does not affect the compound eye. However, eye development can proceed in a complete loss-of-function ey mutant background. Our big question is to understand how the fly’s PAX6 molecules regulate eye development. More specifically, we seek to demonstrate how these molecules cooperate to ensure proper expression of the general morphogen decapentaplegic which is required for proper patterning of the eye. Moreover, we wish to show how a proper balance between the expression levels of ey and toy is required for proper development of the two fly’s visual systems, the ocelli and compound eyes, and dorsal-ventral boundary establishment within the compound eye. Using a set of genetic and molecular tools, we have shown that eye development can proceed in the absence of Ey due to Toy, which binds to and activates Ey targets. We have also shown that Ey plays a previously unknown role early in establishing the anterior dorsal head vertex field, which is the region that later gives rise to the ocelli. Early retraction of Ey from that region is required for proper ocellar and dorsal head vertex development. Finally, we have shown that loss of Ey can lead to a mis-regulation of dorsal-ventral patterning genes in the compound eye.

The Goldilocks effect: proper dosage of PAX6 levels is required for proper retinal differentiation and patterning in Drosophila.