The long-range objective of these studies is to gain an understanding of the developmental factors that lead to the orderly, laminated arrangement of neurons within the visual cortex, and the complex set of interneuronal connections that determine its function. To this end, we have analyzed the visual cortex of the reeler mutant mouse which has a stereotyped abnormality in cell position in cortical structures. We have examined the topography of the visual field representation in the striate cortex (area 17), the connections between striate cortex and extrastriate visual rgions, and the receptive field properties of two identified classes of cortical neurons. All of these studies indicate that the afferent, intracortical and efferent connections of the visual cortex of the reeler mutant are established appropriately despite the abnormality in neuronal position that characterizes reeler cortex. In the present application, we propose to study how neurons achieve normal laminar positions within the developing visual cortex. Are they guided there by radial glia? Do radial glia provide a signal to terminate migration? Has the reeler mutation produced an abnormality in neuron-glia interaction, and can that abnormality be localized to the radial glia or to the migrating neurons? Does the extracellular matrix, which is important in cellular migration and differentiation in many embryonic structures, play a role in the migration of cortical neurons or their processes? To approach these questions, we propose to establish radial glia in tissue culture in a manner that will allow direct observations of neuron-glia interactions during neuronal migration and permit the production of """"""""chimeric"""""""" normal-reeler cultures. Immunofluorescence techniques will be used to determine whether specific extracellular matrix components are present in the visual cortex during development. These two approaches will be correlated by examining the role of extracellular matrix components in promoting neurite outgrowth in vitro.
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