Three sets of experiments are proposed to continue our research on the prenatal development of the mammalian visual system. In the next 5 years we will focus on the normal ontogeny of retinal ganglion cells and their axonal projection patterns. First, we will study the ontogeny of regional specialization within the ganglion cell layer. In these experiments retinal ganglion cells will be identified unequivocally by labeling these neurons following injections of the retrograde tracer horseradish peroxidase into the optic chiasm of fetal animals at known gestational ages. As a result it will be possible to study the spatial and temporal patterns of retinal ganglion cell outgrowth as well as the morphological differentiation of these neurons. This information is essential in order to increase our understanding of the processes underlying the maturation of the retinal ganglion cell layer. In the second set of experiments, the formation of retinal nasotemporal decussation patterns will be studied by injecting different fluorescent tracers (diamidino yellow and rhodamine-labeled microspheres) into the main retinorecipient regions on each side of the brain. This will permit an accurate assessment of the degree of nasotemporal overlap in the distribution of ganglion cells whose axons project to the same or opposite side of the brain. It will also be feasible to determine the presence of bilaterally projecting ganglion cells. In the third set of studies, the topographical organization of developing crossed and uncrossed retinofugal projections will be examined using two complementary anatomical methods. These studies will permit us to assess the degree to which developmental refinements and corrections may contribute to the topographical organization of retinal projections. The immediate significance of this research program is to increase our understanding of the events underlying the normal development of the visual system. These results will also provide new knowledge of general principles governing the development of the mammalian brain.
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