Domain specific function of Cullin-4 to promote cell survival in the ventral eye compartment in Drosophila . Meghana Tare¹, Madhuri Kango-Singh^1,2,3, Amit Singh^1,2,3. 1) Department of Biology, University of Dayton, 300 College Park Drive,Dayton, OH 45469; 2) Premedical Program, University of Dayton, 300 College Park Drive, Dayton OH 45469; 3) Center for Tissue Regeneration and Engineering at Dayton (TREND), University of Dayton, 300 College Park Drive, Dayton OH 45469.

   Axial patterning is required for transition of a monolayer organ primordium to a three-dimensional organ. In the Drosophila eye, the first lineage restriction event of generation of dorsal and ventral compartments is an outcome of domain specific expression and/or function of proteins during early larval development. We identified an ubiquitin ligase cullin-4 (cul-4) as a new member of ventral eye gene hierarchy. Loss-of-function of cul-4 results in the preferential loss of ventral eye cells due to Wg mediated induction of cell death. Wg, acts as a negative regulator of eye development, and is involved in induction of cell death through activation of Caspases as well as JNK signaling pathway. Blocking Wg signaling does not completely rescue cul-4 mutant phenotype. We looked for other targets of Cul-4 in the eye. We found that a transcription factor dE2F1 (a regulator of G1-S transition during cell cycle), a reported target of cul-4, may also be responsible for loss of ventral eye phenotype of cul-4 mutant. It is known that optimum levels of E2F1 are required for growth. Increase/decrease of E2F1 from its optimum levels results in induction of cell death in the developing tissues. Here we present the mechanism by which Wg and dE2F1 are involved in cell survival function of cul-4 in the ventral eye. Our studies will help to discern a novel mechanism by which cell cycle genetic circuitry participate in axial patterning in order to promote cell survival during organogenesis.