NERVE-TARGET CELL INTERACTION IN TASTE BUD MAINTENANCE

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DESCRIPTION (provided by applicant): A key question in taste is how the system maintains a stable message about taste quality while receptor cells are turning over, constantly changing connections between the taste bud and its nerve fibers. To accomplish this the taste periphery must employ a high degree of receptoneural plasticity. We are beginning to understand the neurochemical basis of receptoneural plasticity in relation to the precision with which ganglion cells are connected to taste buds. Plasticity is most dramatic in the degeneration of taste buds when denervated, and their rapid regeneration when reinnervated. Evidence is growing that such neuron-target cell plasticity involves neurotrophins and their tyrosine kinase receptors. In hamster, the fungiform buds of which uniquely resist degeneration after denervation, we identified enrichments in BDNF, TrkB and TrkC not seen in vallate or foliate buds that do not resist denervation, e.g., neurotrophin-positive fungiform bud cells are uniquely unaffected by denervation. Conceivably, cells expressing these growth factors are involved in taste bud maintenance and in promoting nerve fiber in-growth. The possibilities that such maintenance involves increases in gemmal cell genesis to offset cell losses due to denervation, or influences on cell lifespan, will be evaluated by BrdU labeling. A role for neurotrophins in the targeting of nerve fibers will be explored with multicolored lipophilic dyes to demonstrate precisely the connectivity between small populations of ganglion cells and a single buds. Studies of taste bud neurotrophin expression in relation to denervation, reinnervation, gemmal cell genesis, and innervation patterns will emphasize analysis of the mouse. Mouse fungiform buds have uniquely discrete innervation patterns and express neurotrophins differently (e.g., less BDNF) than hamster buds. Species comparison allows formulation of hypotheses about the role of neurotrophins and receptors in taste bud maintenance and innervation. An existing BDNF epithelial overexpressing mouse line will be used to test the hypothesis that increased peri-bud neurotrophin results in denser, less discrete innervation and heightened bud cell genesis or lifespan. For comparison, bud-specific BDNF knockout mice will be generated to specifically test the effect of bud neurotrophin absence on innervation, reinnervation and gemmal cell differentiation. Additionally, an inducible BDNF bud knockout mouse will be generated to test the effect of BDNF loss.