The axons of retinal ganglion cells project to the central visual nuclei in the brain in a topographic pattern, such that the two dimensional pattern of the ganglion cells in the retina is approximately recreated in the pattern of their terminals in the visual nuclei. Alterations in the projection pattern of ganglion cell axons result in ineffective processing of visual information and an inability to respond to visual stimuli in a meaningful manner. The mechanism responsible for development of this orderly pattern of connections is unknown. One hypothesis suggests the existence of two orthogonal gradients of molecules on the axons of retinal ganglion cells that would impart positional Information to these cells. The interaction between positionally labeled retinal axons and tectal cells with complimentary labels could determine the pattern in which connections develop. Several molecules have been identified in a dorsal-ventral concentration gradient in the developing retina. One or more of these molecules may be responsible for positional labels on retinal ganglion cells in this axis of the retina. No molecules have been definitively identified in the developing retina that could supply positional information on cells in the nasal-temporal axis. A monoclonal antibody was recently developed that recognizes in chick a cell surface antigen on temporal retinal axons, TRAP (for temporal retinal axon protein). TRAP appears to be absent from most nasal retinal axons in the developing retina. This study will characterize in a quantitative fashion the distribution of TRAP in the visual system of the developing chick. Antibodies to TRAP will also be used in several assays to test whether this antigen is responsible for positional labels on retinal axons in the nasal-temporal axis. Tissue culture studies suggest the existence of unique antigens on nasal retinal axons as well as os temporal retinal axons. The next goal of this study will be to generate monoclonal antibodies to unique antigens of nasal retina. The antibodies will be used to characterize the antigens. Finally immunohistochemical studies using the antibody to TRAP revealed a decussation of nasal and temporal retinal axons in the optic nerve head of the chick. This is inconsistent with previous descriptions of the topography of retinal axons in the optic pathway. In order to understand how nasal and temporal retinal axons interact with one another in development, it is necessary to have a clear picture of how they are positioned relative to one another. This study will determine the topography of retinal axons in the optic nerve, chiasm and tract of the developing chick. This will involve the three dimensional reconstruction of axons labeled with anterogradely transported markers and antibodies to TRAP.
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