An understanding of the development of the vertebrate retina is of fundamental importance to our understanding of disease and to the generation of effective therapies for blinding illnesses. For example, replacement of degenerating photoreceptors will rely upon manipulation of the progenitor cells that make photoreceptors. A clear description of the number and types of progenitor cells that make up the retina will provide a platform from which mechanistic studies can be done. We and others showed many years ago that retinal progenitor cells are multipotent throughout development (progenitor cells are herein defined as cycling cells). We subsequently showed that even though they are multipotent, they are not equivalent throughout development. Over the last grant period we examined these cells further with respect to their cell cycle behavior. These studies provided additional evidence that retinal progenitor cells differ as they express different cell cycle regulatory proteins and use them to control cell cycle exit in different populations. We now wish to further define the number and types of retinal progenitor cells. These data will rule in or out several different models of retinal development. Further, we wish to use these data to generate strains of mice in which different types of progenitor cells will be differentially marked with reporter genes. These strains will be used to further our understanding of how retinal progenitor cells transition from one state to the next, and whether different types of progenitors vary in their proliferative behavior and/or production of different cell types.
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