Photoreceptors are the highly specialized sensory neurons that carry out the first step in vision. The mechanisms for the production of photoreceptors during development are of interest from both a basic science and a therapeutic viewpoint. Photoreceptors, particularly rods, the cells that mediate vision in dim light, are the cell type most often directly affected by genetic diseases that lead to blindness. Cone photoreceptors, which mediate our daylight and color vision, also die due to genetic and environmental causes. Replacement of dying photoreceptor cells will require knowledge of the mechanisms of their genesis. For example, stem cells can be instructed to produce rods and/or cones prior to engraftment. In addition, an understanding of photoreceptor development might lead to interventions that prevent developmental abnormalities, which lead to blindness. We propose to investigate the mechanisms by which photoreceptors are generated. The focus will be on the transcription factors that are required for photoreceptor production, including an analysis of their upstream regulators and downstream targets. State-of-the-art nucleic acid technologies that build on our previous genomic studies, as well as our newly developed methods for the study of gene regulation, will be carried out. PUBLIC HEALTH RELEVANCE: Photoreceptors are the highly specialized sensory neurons that carry out the first step in vision. They are often the target of genetic diseases that lead to blindness. We propose to study the mechanisms for the production of photoreceptors, which can lead to the prevention of developmental abnormalities and/or therapies employing engraftment of photoreceptor cells produced by stem cells.