A role for Ebi in neuronal cell cycle control

Mutations in ebi were isolated as enhancers of an over-proliferation phenot ype generated by elevated E2F/DP activity in the Drosophila eye, ebi allele s also strongly suppress a phenotype caused by the cyclin-dependent kinase inhibitor p21, restoring S phases in the second mitotic wave of the develop ing eye disk. ebi mutant embryos display ectopic S phases within the periph eral nervous system and central nervous system at a time in development whe n neuronal precursor cells would normally begin to differentiate. Consisten t with this, we find that ebi mutants have a reduced capacity to undergo ne uronal differentiation, that Ebi physically interacts with Sina and phyllop od, and that Ebi promotes Ttk88 degradation in vitro and in S2 cells. Ectop ic expression of Ttk88 inhibited differentiation in embryos and eye discs; however, this block to differentiation was insufficient to promote S phase entry in either of the situations where ebi mutations gave this effect. We conclude that Ebi has two distinct functions; it promotes the degradation o f a repressor of neuronal differentiation (Ttk88), and has a second indepen dent function that limits S phase entry.