Rb Regulates Proliferation and Rod Photoreceptor Development in the Mouse Retina

Abstract

Abstract: : The retinoblastoma (Rb) protein regulates proliferation, cell fate specification and differentiation in the developing central nervous system. However, the role of Rb in the developing mouse retina has not been studied, because Rb–deficient embryos die before the retinae are fully formed. Purpose:We have combined several genetic approaches to explore the role of Rb in regulating proliferation, apoptosis, cell fate specification and differentiation in the mouse retina. Methods: Retinae from Rb knockout E13.5 embryos were explant cultured for 12 days. Proliferation, apoptosis, cell fate specification and differentiation were analyzed in these retinal explants. To extend the explant culture studies, Rb was conditionally knocked out in the reitna using the Rb–lox mice crossed to two different Cre–transgenic mouse lines (Chx10–Cre and Mox–Cre). To determine which of the roles of Rb in retinal development were cell autonomous we injected a Cre–expressing retrovirus into the eyes of newborn Rb–lox mice to generate clones of cells lacking Rb in vivo. Results: During postnatal development, Rb is expressed in proliferating retinal progenitor cells and differentiating rod photoreceptors. In the absence of Rb, progenitor cells continue to divide, and rods fail to mature. Both of these roles were found to be cell autonomous using the Cre retrovirus. Conclusions: Taken together we have found that Rb plays two distinct roles during reitnal development regulating proliferation and rod photoreceptor maturation.  

Keywords: photoreceptors • proliferation • genetics