Abstract:
Previously, we have presented data describing the redundant and compensatory roles of the Retinoblastoma family members (Rb, p107, and p130) in controlling murine retinal development. Recently, we have observed that redundancy and compensation are not sufficient to explain the entire scope of the Rb family’s role in retinal development. A series of experiments have been performed to identify distinct roles of Rb and p107 in the developing retina. We analyzed retinae from Rb family knockout mice and Rb conditional knockout mice that were mated to a retina specific Cre transgenic mouse or injected with a Cre expressing retrovirus. Retinal analyses included real–time RT–PCR, micro–array hybridization, immuno–histochemistry for retinal cell–type markers, and electron microscopy. We have determined that in the developing retina, Rb and p107 possess unique and distinct functions in addition to their previously identified redundant and overlapping functions. More specifically, the role of p107 seems to be restricted to regulation of proliferation while Rb serves a broader role in regulation of both proliferation and differentiation. Also, in the absence of Rb and p107 adult retinal cells express progenitor markers, such as Pax–6, and maintain an immature, progenitor–like morphology (see figure). This model and experimental approach provides an ideal system for investigating the specific roles played by individual members of the cell cycle machinery.
Keywords: retinal development • retinoblastoma • gene/expression