Brain development requires the orderly generation of numerous distinct types of neurons, establishment of complex cell-cell connections, and remodeling of neuronal processes in response to experience. In order to investigate the molecular mechanisms underlying brain development and plasticity, I would like to study how a tiny larval brain of the Drosophila grows enormously and evolves into a much more sophisticated brain after large-scale remodeling of its neural circuits. Understanding how neuronal progenitors can give rise to distinct types of neurons in a functional brain is important for future cell replacement therapies in human brains. Identification of molecules involved in remodeling of neuronal processes may further elucidate how to manipulate neural circuits in our brains. I propose to study the post-embryonic development of the Drosophila central nervous system from three distinct angles. In the first aim, I will conduct extensive genetic screens to identify genes required for development of the mushroom bodies that form the insect learning and memory center. Mushroom body neurons that are homozygous for a random mutation will be created and analyzed in otherwise wild-type organisms. This approach has led to identification of the ultraspiracle (usp), which encodes one subunit of the ecdysone receptor, as an essential gene for pruning of larval-specific processes during neuronal remodeling. In the second aim, I will directly test the hypothesis that the insect hormone ecdysone orchestrates various aspects of the post-embryonic neuronal development. Mosaic approaches will be used to examine roles of USP in both post-embryonic neurogenesis and morphological differentiation of adult-specific neurons. In the third aim, I would like to identify molecular markers that are specific for distinct types of neurons and their precursors during the post-embryonic development, which will greatly facilitate future molecular genetic studies in the complex nervous system.
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