Homeodomain interacting protein kinase promotes normal and ectopic eye development through the repression of pax6 paralogs twin of eyeless and eyeless.

Homeodomain interacting protein kinase promotes normal and ectopic eye development through the repression of pax6 paralogs twin of eyeless and eyeless. Jessica A Blaquiere¹, Wendy Lee^1,2, Esther M Verheyen¹. 1) Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada; 2) Dermatology and Cell Biology, NYU Langone Medical Center and School of Medicine, New York University, New York, NY, USA.

The retinal determination gene network (RDGN) encompasses a group of nuclear factors responsible for mediating eye development. Pax6 paralogs Twin of eyeless (Toy) and Eyeless (Ey) sit atop this network. A striking feature common to most RD factors is their ability to coax non-retinal tissue to adopt retinal fate upon mis-expression. We further investigate the mechanism of ectopic eye development, specifically in the leg by using dpp-GAL4, UAS-toy. We utilized toy in our assay due to our interest in examining the Ey domain within the presumptive ectopic eye field; although in an exogenous tissue, Ey is under control of its endogenous promoter. Interestingly, we found much like the normal eye, Ey must be restricted away from developing photoreceptors (PRs) for them to be specified. This observation led us to identify a morphogenetic furrow within the ectopic eye field and to the conclusion that ectopic eye development is progressive in nature exactly like the normal eye. In addition, we provide further evidence that Ey is a repressor of PR differentiation and highlight the importance of Ey repression for normal and ectopic eye development to occur. Using genetic analyses we have identified Homeodomain interacting protein kinase (Hipk), a serine-threonine kinase, as a transcriptional repressor of both toy and ey. We have previously shown that Hipk promotes Notch (N) mediated growth of the eye disc by repressing the global co-repressor Groucho and here, we provide evidence that Hipks involvement with toy/ey is separate from its role in the N pathway. Both loss-of-function and over-expression experiments reveal that Hipk represses toy and ey in the eye-antennal disc and this relationship is in fact conserved in the ectopic eye. Collectively, our data suggests Hipk promotes normal and ectopic eye development by repressing toy/ey.