Trichromatic color vision in diurnal primates, including humans, is mediated by a retinal mosaic of three subtypes of photoreceptors, the red-,green-,and blue-sensitive cones, whose visual pigments are maximally sensitive to long, middle and short wavelengths, respectively. The goal of this research is to obtain insight into the cellular events that underlie the phenotypic specification of these opsin-specific cone subtypes in the primate retina. Recent studies suggest that cell phenotypes are specified in part by two mechanisms: the time of a cell's final mitotic division, and local cell: cell interactions. Whether or not these same mechanisms are important for the specification of the cone subtypes is unclear. The experiments presented in this proposal will use a combination of in vivo and in vitro techniques to investigate the contribution of these two basic processes to the development of the ratio and reiterative distribution of red/green-and blue-sensitive cones in the retinal mosaic. Two interrelated sets of experiments are proposed. The first group of experiments will examine the relationship between a cone's birthdate and its eventual opsin-specific phenotype by combining 3H thymidine-autoradiography and post-embedding immunocytochemistry to identify the birthdate and opsin phenotype of individual cones in the fetal monkey retina. The second set of experiments will assess the influence of diffusable and/or contact-mediated cell interactions on the expression of the wavelength-specific photopigments by immature, postmitotic cones. These in vitro experiments will take specific advantages of the unique segregation of the cone subtypes in the mouse retina by co-culturing prospective blue-sensitive cones of the ventral mouse retina with dorsal retina which contains a high percentage of red/green- sensitive cones. Quantitative data obtained from these dual lines of research may provide important insight into the roles of specific development mechanisms and pattern formation in the mammalian retina, as well as abnormalities of the development of the human photoreceptors mosaic.
