Formation of photoreceptors during embryogenesis involves precise regulation of expressed genes. Although several transcription factors that are involved in photoreceptor differentiation have been identified, the direct targets of these genes as well as their regulators remain largely unknown. Understanding the regulatory mechanisms of cone vs. rod specific gene expression is one of the central issues of this proposal. Specifically, we will study molecular aspects of Nrl, Nr2E3 and Mef2C function and determine whether they can directly regulate photoreceptor cell fate. The specific aims of this proposal are to: (1) establish whether Nrl and/or NR2E3 can reprogram retinal precursors to become rods (2) determine whether Nrl directly activates NR2E3 (3) determine whether Mef2C restricts Nrl expression to photoreceptors. Successful completion of this project will improve our understanding of photoreceptor development by providing additional regulatory mechanisms for cell specific gene expression. [unreadable] [unreadable]