Vertebrate photoreceptors (PR) are sensory neurons and their physiological role in vision depends on the proper development of the outer segment (OS). We are addressing a central unanswered issue in vision research: the role of retinal pigment epithelium (RPE) in the terminal differentiation of PR. Our central hypothesis is that maturation of the apical surface of RPE, composed of very long apical microvilli (MV) (~20 ?m), is critical for the normal development of PR OS. We are employing an innovative approach that integrates cell biology and genetics and utilizes a novel RPE-PR co-culture model, to address my specific aims. This project has strong potential for major advances in vision research and important implications for human retinal diseases.