BRAIN DEVELOPMENT INJURY REPAIR

The role of neuron-astroglial relationships in the development of the normal and injured mammalian brain will be analyzed. The shape and cytoskeletal organization of astroglia in cerebral and cerebellar cortex, regions where astroglia are thought to guide neuronal migration, will be analyzed in the embryonic mouse brain and compared with that of astroglia in the brainstem and spinal cord, regions where an architectonic role for astroglia has not yet emerged, and with optic nerve, an area where immature astroglia might guide axon growth. Neuron-astroglial interactions of cells from various regions will be analyzed, and purified neurons and astroglia from different brain regions and ages will be "mixed and matched" in vitro to assess whether different types of astroglia are present during development and, if so, whether they relate to the region of origin of the astroglia or to their architectonic function. To analyze the formation of neuron-glial associations, the formation, extension and interactions of glial growth cones would be studied using biochemical, immunological and cell biological approaches. The expression of glial filament proteins will be studied using a newly developed cDNA probe for the glial filament protein using both microinjection and in situ hybridization approaches. The interactions of the various components of the astroglial cytoskeleton will be investigated as they relate to celluilar differentiation and function. The insights and tools obtained in the basic biological invetigations of the project will be utilized to understand the cell biology of astroglial reactivity or 'gliosis' after injury to the CNS and to determine the effects of antibodies against astroglial surface macromolecules on the development of the brain, using both the intact embryo and reaggregate cultures of the cerebellum as models. These same tools will be used to study the surfaces of astroglia in neural regeneration.