NOS/CGKI PATHWAY AND DEVELOPMENT OF CHICK DRG

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Nitric oxide (NO) is a major regulator of physiological function. It can indirectly activate cGMP-dependent kinase (cGK) by activating guanylyl cyclase. Reports suggest that NO and cGks may play a role in sensory signaling and development. Neuronal NO synthase (NOS)is transiently expressed by dorsal root ganglia (DRG) neurons in the rat embryo. In addition, cGKI has also been localized to a subpopulation of DIG neurons in rats. However, the actual role that these two enzymes may play in DRG development has not been studied. Recent studies have defined a role for NO in neurotoxicity. NO reacts with superoxide to form peroxynitrate. This peroxynitrate is thought to induce apoptosis or necrosis in cortical cells or PC12 cells. It has also been shown that NO halts the growth of neurites in cultures of DRG neurons. Thus, it is possible that the NOS/cGK pathway plays a role in DRG development by regulating cell survival and axon outgrowth. This proposal aims to use the chick embryo as a model for studying the effects of activators and inhibitors of NOS and cGK during development. The first set of experiments are focused at determining the temporal expression of NOS and cGKI in chick DRG. Using these results , the second set of experiments will define the role for NOS and cGKI in survival and neurite outgrowth of cultured DRG. The third set of experiments use pharmacological agents to elucidate a role for the NOS/cGKI pathway in development of chick DRG in vivo. Taken together, the results form the three sets of experiments will elucidate NOS/cGK function in developing DRG.