Brain development involves orderly generation of distinct types of neurons, establishment of stereotyped neuronal connections, and developmentally programmed as well as activity-dependent remodeling of neuronal projections. In addition, like neurons, glial cells are integral to both formation and function of the brain. To elucidate the molecular mechanisms governing brain development, we propose to continue studying post-embryonic development of the Drosophila brain that involves various interesting developmental phenomena, such as extensive neurogenesis and gliogenesis in functional neural circuits and large-scale remodeling of neural circuits during metamorphosis. First, we will identify additional molecules required for various aspects of post-embryonic development of the Drosophila brain via isolating and characterizing more mushroom body mutants. Second, we will investigate whether and how numerous distinct DSCAM molecules operate collaboratively and/or differentially to mediate diverse cell type-specific neuronal morphogenesis. Third, we will develop novel MARCM technology for examining post-embryonic neurogenesis and gliogenesis systematically and simultaneously. Studying post-embryonic development of the Drosophila brain promises to shed new light on how complex neural circuits form in human brains. In particular, we expect to gain novel insights into the molecular mechanisms that govern (1) derivation of different types of neurons from common precursors, (2) chronologically appropriate neuronal morphogenesis, (3) formation/extension/guidance/arborization of dendrites versus axons, (4) remodeling of neuronal projections, (5) diverse cell type-specific neuronal morphogenesis, and (6) neuron-glial interactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS042049-10
Application #
7660443
Study Section
Neurogenesis and Cell Fate Study Section (NCF)
Program Officer
Riddle, Robert D
Project Start
2001-08-01
Project End
2010-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
10
Fiscal Year
2009
Total Cost
$356,309
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Biology
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
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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