08-P011 A dsRNA genetic screen to identify regulators of intracellular traffic in the Notch signalling pathway

hypothesis, we used the Cre-loxP system to conditionally inactivate Numb and its homolog Numblike in RPCs at different stages of retinogenesis. We used retroviral vectors expressing Cre recombinase and a reporter to infect Numb/Numblike floxed mouse retinas at early (E13) and late (P0) stages of retinal development. Analysis of cell composition of the resulting knockout clones showed that Numb inactivation at E13 prevented RPC cycle progression, but did not affect self-renewing asymmetric cell divisions. In contrast, late inactivation of Numb did not affect RPC proliferation, but drastically reduced terminal asymmetric cell divisions that give rise to a photoreceptor and another cell type. These results indicate that Numb function changes over time in the developing mouse retina.