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The Retinoblastoma (RB) gene was first identified as a tumor suppressor in humans, but is evolutionary conserved in multicellular eukaryotes. This project uses genetic and functional genomics approaches to investigate the regulatory function and significance of the plant Retinoblastoma-related protein in cell cycle control, cell differentiation and development using Arabidopsis as a model system. BackgroundThe Retinoblastoma gene (RB) is of high medical interest as a tumor suppressor and the focus of considerable research efforts because of its role in tumor formation. But efforts to unravel the mechanism by which pRB acts as a tumor repressor in mammalian cells have been complicated by functional redundancies and implication of pRB in a wide variety of cellular processes. The best understood functions of pRB are the regulation of the E2F transcription factor during the transition from G1 to S phase and regulation of a few key differentiation factors, but the biological significance of interactions with many other proteins remains unclear. We discovered that the RB pathway is conserved in plants and that the RB-related plant homolog (RBR) is essential during the mitotic arrest of the female gametophyte prior to fertilization. Loss of RBR function therefore affects plant development much earlier than was previously known from the RB knock-out mouse. In this project we investigate the function of the Arabidopsis RBR gene and protein in coordinating cell division activity with cell specification and developmental processes.Scientific GoalUsing targeted loss- and gain-of-function approaches in combination with functional genomics technologies we dissect the RBR pathway in Arabidopsis to understand how RBR controls stem cell maintenance in the plant meristem, in which cells divide to form all post-embryonic organs of the plant. Specifically, we expect to identify novel regulatory mechanisms in stem cell control and genes targeted by the RBR pathway. This will lead us to proteins that interact with RBR and have critical functions in connecting RBR as a regulator of cell cycle activity to cell specification and differentiation during development.SignificanceSince RBR is encoded by a single gene in Arabidopsis and most of plant development is post-embryonic, the Arabidopsis RBR gene represents a unique and genetically powerful system to advance our understanding of the RB/RBR pathway and its regulatory function in connecting cell cycle control to differentiation and development. Our proposed project will provide new insights that may facilitate clinically relevant research and new agricultural applications.
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