How the brain is organized into the neuronal circuits that carry out the processing of visual information has long been in question. In the brain of Drosophila, photoreceptor cell axons and the cortical axons of the optic ganglia form precise topographic interconnections. We are using a genetic approach to identifying the molecules involved in the establishment of this connective architecture. A genetic screen for defects in the establishment of neuronal connectivity in the visual system resulted in the recovery of mutations at fifty-seven loci. Included in this collection are mutations that affect the signaling mechanisms underlying the assignment of cell fate in the visual primordia, and interactions between axons and prospective target cells during the establishment of connectivity. We will: 1) study the function of a Drosophila member of the Cytohesin family in controlling the response of neuronal precursor cells to retinal axon-borne differentiation signals, 2) conduct a small-scale screen for loci involved in the generation of axonal connectivity based on protein localization reported by a GFP gene-trap transposon, 3) perform a screen for mutations that disrupt the local fine structure of lamina synaptic circuitry and characterize some of the loci identified, 4) isolate mutations at the eph and ephrin loci, and examine their consequences for nervous system development. Given the conservation between the mechanisms that pattern the nervous systems of vertebrates and invertebrates, these studies will likely yield important insights into the development of the complex architectures of the brains of vertebrates, including humans.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY010112-12
Application #
6910628
Study Section
Special Emphasis Panel (ZRG1-MDCN-7 (01))
Program Officer
Oberdorfer, Michael
Project Start
1993-08-01
Project End
2006-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
12
Fiscal Year
2005
Total Cost
$278,950
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Dearborn Jr, Richard E; Dai, Yong; Reed, Brian et al. (2012) Reph, a regulator of Eph receptor expression in the Drosophila melanogaster optic lobe. PLoS One 7:e37303
Chu, Tehyen; Chiu, Michael; Zhang, Elisa et al. (2006) A C-terminal motif targets Hedgehog to axons, coordinating assembly of the Drosophila eye and brain. Dev Cell 10:635-46
Ashraf, Shovon I; Kunes, Sam (2006) A trace of silence: memory and microRNA at the synapse. Curr Opin Neurobiol 16:535-9
Yang, Hong; Kunes, Sam (2004) Nonvesicular release of acetylcholine is required for axon targeting in the Drosophila visual system. Proc Natl Acad Sci U S A 101:15213-8
Dearborn Jr, Richard; He, Qi; Kunes, Sam et al. (2002) Eph receptor tyrosine kinase-mediated formation of a topographic map in the Drosophila visual system. J Neurosci 22:1338-49
Song, Y; Chung, S; Kunes, S (2000) Combgap relays wingless signal reception to the determination of cortical cell fate in the Drosophila visual system. Mol Cell 6:1143-54
Kunes, S (2000) Axonal signals in the assembly of neural circuitry. Curr Opin Neurobiol 10:58-62
Atkinson, J; Panni, M K (1999) Optic target regulation of NADPH-diaphorase by larval retinal axons in Drosophila. Neurosci Lett 262:21-4
Huang, Z; Shilo, B Z; Kunes, S (1998) A retinal axon fascicle uses spitz, an EGF receptor ligand, to construct a synaptic cartridge in the brain of Drosophila. Cell 95:693-703
Huang, Z; Kunes, S (1998) Signals transmitted along retinal axons in Drosophila: Hedgehog signal reception and the cell circuitry of lamina cartridge assembly. Development 125:3753-64

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