The goal of this project is to test the validity of two general hypotheses: (1) the growth cone reprogramming hypothesis, and (2) the unique dendritic guidance hypothesis. According to the first hypothesis, axon guidance occurs through an interactive reprogramming model, in which a growth cone must encounter specific molecular cues early during its navigation so that it can undergo a reprogramming process that enables it to properly respond to cues presented subsequently. The project adopts in vivo single cell analysis, while taking the CNS midline as one example of early guidance cues that may be responsible for growth cone reprogramming. The second hypothesis is a model to explain why dendrites and axons grow differently. According to this hypothesis, axons and dendrites grow differently because they use a different set of growth cone receptor/signaling molecules. A neuron is capable of targeting molecules differentially to its axon or dendrites, thereby allowing the differential expression of receptors at each site. Additional possibilities are that dendritic growth may depend on axonal guidance, or that dendritic growth cones may be more susceptible to neuronal activity. This project will begin to tease apart the unique dendritic guidance hypothesis by using in vivo single cell analysis of dendritic development as compared to axonal development. It is anticipated that the present study will provide a better understanding of operational principles of growth cone guidance.
