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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-MDCN-6 (01))
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Gwinn, Katrina
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University of Illinois Urbana-Champaign
Schools of Arts and Sciences
United States
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Lee, Tzumin (2014) Generating mosaics for lineage analysis in flies. Wiley Interdiscip Rev Dev Biol 3:69-81
Yang, Jacob S; Awasaki, Takeshi; Yu, Hung-Hsiang et al. (2013) Diverse neuronal lineages make stereotyped contributions to the Drosophila locomotor control center, the central complex. J Comp Neurol 521:2645-Spc1
Yu, Hung-Hsiang; Awasaki, Takeshi; Schroeder, Mark David et al. (2013) Clonal development and organization of the adult Drosophila central brain. Curr Biol 23:633-43
Awasaki, Takeshi; Huang, Yaling; O'Connor, Michael B et al. (2011) Glia instruct developmental neuronal remodeling through TGF-? signaling. Nat Neurosci 14:821-3
Awasaki, Takeshi; Lee, Tzumin (2011) New tools for the analysis of glial cell biology in Drosophila. Glia 59:1377-86
Kao, Chih-Fei; Lee, Tzumin (2010) Birth time/order-dependent neuron type specification. Curr Opin Neurobiol 20:14-21
Lin, Suewei; Lai, Sen-Lin; Yu, Huang-Hsiang et al. (2010) Lineage-specific effects of Notch/Numb signaling in post-embryonic development of the Drosophila brain. Development 137:43-51
Yu, Hung-Hsiang; Chen, Chun-Hong; Shi, Lei et al. (2009) Twin-spot MARCM to reveal the developmental origin and identity of neurons. Nat Neurosci 12:947-53
Jensen, Philip A; Zheng, Xiaoyan; Lee, Tzumin et al. (2009) The Drosophila Activin-like ligand Dawdle signals preferentially through one isoform of the Type-I receptor Baboon. Mech Dev 126:950-7
Yu, Hung-Hsiang; Yang, Jacob S; Wang, Jian et al. (2009) Endodomain diversity in the Drosophila Dscam and its roles in neuronal morphogenesis. J Neurosci 29:1904-14

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