For a nervous system to be wired properly, the axons have to be guided toward the correct targets and the dendrites need to have the correct branching pattern. At present, much less is known about the molecular mechanisms that control dendrite branching as compared to those that control axon guidance. The goal of this proposal is to use Drosophila genetics to identify """"""""Core programs"""""""" that control dendrite development. For this purpose, recently, we developed and further refined a simple assay system. By using fly transgenic technique, we express Green Flourescent Protein (GFP) in specific classes of multiple dendritic (MD) neurons, a group of sensory neurons with class-specific dendritic branching pattern. This allows us to visualize the development of the dendrites of MD neurons in the living fly embryos and thereby provides an excellent assay system for a genetic dissection of dendrite development. We have used this assay system to identify and characterize dendrite mutants and have already made considerable progress in identifying """"""""Key genes"""""""" that control different aspects of dendrite development and have begun to gain mechanistic insights. We propose to extend this work by doing a systematic and near saturation screen to identify the great majority of the genes that are required to control the dendrite development in Drosophila. We will carry out in depth phenotypic and molecular studies of the """"""""Key genes"""""""" identified from this mutant screen. These Key genes should lead to the identifications of """"""""Core programs"""""""" that control dendrite development. Given the striking conservation of many molecular mechanisms that control various developmental processes including axon guidance, it is highly likely that the molecular mechanisms controlling dendrite development is conserved between fly and mammals. The Core programs identified from this work will contribute to the understanding and eventual treatment of human neurological diseases many of which have pathology in dendrites. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS040929-06
Application #
6986764
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Riddle, Robert D
Project Start
2001-01-18
Project End
2009-11-30
Budget Start
2005-12-01
Budget End
2006-11-30
Support Year
6
Fiscal Year
2006
Total Cost
$342,111
Indirect Cost
Name
University of California San Francisco
Department
Physiology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Jin, Peng; Bulkley, David; Guo, Yanmeng et al. (2017) Electron cryo-microscopy structure of the mechanotransduction channel NOMPC. Nature 547:118-122
Ori-McKenney, Kassandra M; McKenney, Richard J; Huang, Hector H et al. (2016) Phosphorylation of ?-Tubulin by the Down Syndrome Kinase, Minibrain/DYRK1a, Regulates Microtubule Dynamics and Dendrite Morphogenesis. Neuron 90:551-63
Meltzer, Shan; Yadav, Smita; Lee, Jiae et al. (2016) Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons. Neuron 89:741-55
Zhang, Wei; Cheng, Li E; Kittelmann, Maike et al. (2015) Ankyrin Repeats Convey Force to Gate the NOMPC Mechanotransduction Channel. Cell 162:1391-403
Kim, Woo Jae; Jan, Lily Yeh; Jan, Yuh Nung (2013) A PDF/NPF neuropeptide signaling circuitry of male Drosophila melanogaster controls rival-induced prolonged mating. Neuron 80:1190-205
Parrish, Jay Z; Xu, Peizhang; Kim, Charles C et al. (2009) The microRNA bantam functions in epithelial cells to regulate scaling growth of dendrite arbors in drosophila sensory neurons. Neuron 63:788-802
Yang, Chung-Hui; Rumpf, Sebastian; Xiang, Yang et al. (2009) Control of the postmating behavioral switch in Drosophila females by internal sensory neurons. Neuron 61:519-26
Lee, Hsiu-Hsiang; Jan, Lily Yeh; Jan, Yuh-Nung (2009) Drosophila IKK-related kinase Ik2 and Katanin p60-like 1 regulate dendrite pruning of sensory neuron during metamorphosis. Proc Natl Acad Sci U S A 106:6363-8
Kim, Michael D; Wen, Yuhui; Jan, Yuh-Nung (2009) Patterning and organization of motor neuron dendrites in the Drosophila larva. Dev Biol 336:213-21
Wildonger, Jill; Jan, Lily Yeh; Jan, Yuh Nung (2008) The Tsc1-Tsc2 complex influences neuronal polarity by modulating TORC1 activity and SAD levels. Genes Dev 22:2447-53

Showing the most recent 10 out of 34 publications