The overall objective of this research is to describe the molecular mechanisms that regulate cerebellar granule cell maturation. This project focuses on the role of neurotransmitters in the induction of neuronal differentiation during neuron-glial interaction in mouse cerebellar development. 1. The investigators will characterize the signal transduction cascade by which L-glutamate, presumably released from granule neurons, stimulates astroglial cells to release taurine, which in turn stimulates granule neurons. This will be studied in in vitro systems that allow analysis and manipulation of neuronal migration and aggregation. The neurological mutant mouse "weaver", which has deficient concentrations of glutamate and taurine during development, will be used as a model. 2. The investigators will subsequently determine which cell types synthesize and take up taurine, by means of immunocytochemistry and autoradiography. 3. The induction of the protooncogenes c-fos and c-myc by taurine and glutamate will be studied during early postnatal development. C-fos induction will be related to the ability of taurine to prevent cell death in weaver and after excitotoxic reactions.
