The applicant proposes to continue studies of factors that control the pattern of connections between the retina and central visual centers in the brain during development. The applicant has in recent years directed the majority of her attention to the study of retinoids in the developing retina, since there is reason to believe that these molecules may be involved in the developmental of positional identity in the nervous system, including that which is likely to be involved in map formation. In the previous grant period, the applicant has contributed substantially to this field in several ways, including the development of a novel technique for quantifying retinoids in tissues, and the identification of three different retinoic acid (RA) synthetic activities: AHD2, a non- specific aldehyde dehydrogenase located primarily in the dorsal retina; V2, which they have recently cloned and looks to be the first member of a new class of RA synthetases; and V1, the primary synthetic activity in the ventral retina, that looks to be distinct from the other two enzymes on the basis of substrate selectivity and response to inhibitors. The applicant has also discovered that retinoic acid is generated in the mature retina in response to light, a potential mechanism by which light can act on gene transcription via RA receptors. In this proposal, the applicant will continue these lines of investigation, with the following specific aims: (1) look for differences in the regulation of retinaldehyde dehydrogenases by CRBP as a potential explanation for their diversity; (2) identify V1, the enzyme in the ventral retina responsible for RA synthesis; (3) identify a novel 60 kDa membrane-associated molecule differentially expressed in the ventral retina; (4) further characterize the light-induced synthesis of RA in mature retina that they have recently described; (5) compare the relative concentrations of RA in retina and pigment epithelium in developing mice, RCS rats and vitiligo mice; and (6) examine the relationship between monocular enucleation and retinaldehyde dehydrogenase levels in the visual cortex in mice.
Showing the most recent 10 out of 38 publications
