The overall goal of this application is to understand the transformation of a motile growth cone into a sedentary synapse. We will use the Drosophila giant fiber (GF) system as a model to study the way in which a single axon recognizes the target area and makes a synapse with appropriate partners. Through targeted gene expression in the GF and its synaptic partners, we will explore the molecular aspects of this dynamic transformation. Our hypothesis is that semaphorin1a, which is well known for its role as a ligand during pathfinding, has a second role as a receptor during synaptogenesis and that it is critical to the delicate and dynamic molecular interactions that control the transition from growth cone to synapse. In order to better understand this new role for semaphorin1a, we will dissect the intracellular domain of semaphorin1a and determine its function during synapse formation. We will also examine putative downstream signals and will focus on enabled as a potential partner for semaphorin1a in stopping the growth cone. Finally, we will assay the dynamic regulation of proteins like semaphorin1a by the ubiquitin cascade. One of the first mutants isolated in the Drosophila giant fiber system was bendless, a defect in an E2 component of the ubiquitin cascade that causes a defect in the maturation of the giant synapse. We propose to revisit these early findings to assess the targets for the ubiquitin cascade and how they contribute to the dynamic processes that underlie the transition from growth cone to synapse.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS044609-05
Application #
7107881
Study Section
Special Emphasis Panel (ZRG1-SSS-P (01))
Program Officer
Riddle, Robert D
Project Start
2002-08-01
Project End
2010-05-31
Budget Start
2006-06-01
Budget End
2010-05-31
Support Year
5
Fiscal Year
2006
Total Cost
$262,684
Indirect Cost
Name
Florida Atlantic University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
004147534
City
Boca Raton
State
FL
Country
United States
Zip Code
33431
Godenschwege, Tanja A; Murphey, Rodney K (2009) Genetic interaction of Neuroglian and Semaphorin1a during guidance and synapse formation. J Neurogenet 23:147-55
Uthaman, Smitha B; Godenschwege, Tanja A; Murphey, Rodney K (2008) A mechanism distinct from highwire for the Drosophila ubiquitin conjugase bendless in synaptic growth and maturation. J Neurosci 28:8615-23
Allen, Marcus J; Godenschwege, Tanja A; Tanouye, Mark A et al. (2006) Making an escape: development and function of the Drosophila giant fibre system. Semin Cell Dev Biol 17:31-41
Godenschwege, Tanja A; Kristiansen, Lars V; Uthaman, Smitha B et al. (2006) A conserved role for Drosophila Neuroglian and human L1-CAM in central-synapse formation. Curr Biol 16:12-23
Murphey, R K; Froggett, Stephan J; Caruccio, Phyllis et al. (2003) Targeted expression of shibire ts and semaphorin 1a reveals critical periods for synapse formation in the giant fiber of Drosophila. Development 130:3671-82
Godenschwege, Tanja A; Hu, Hailan; Shan-Crofts, Xiaoliang et al. (2002) Bi-directional signaling by Semaphorin 1a during central synapse formation in Drosophila. Nat Neurosci 5:1294-301