We have recently identified the Drosophila receptor Dscam and shown that it is essential for the formation of proper connectivity in the fly nervous system. Dscam is a member of the immunoglobulin superfamily and is highly related to the human protein """"""""Down syndrome cell adhesion molecule"""""""" (DSCAM). The Drosophila Dscam gene is extraordinarily complex and can generate some 38,000-protein isoforms through alternative splicing. The overall goal of our studies is to test the hypothesis that alternative splice isoforms of the Dscam receptor constitute a molecular recognition code for synaptic specificity. We will use genetic and molecular approaches to functionally test the importance of neuronal receptor diversity. We propose that the extraordinary molecular diversity of Dscam provides a paradigmatic and genetically accessible case for systematically dissecting the mechanism by which neuronal receptors contribute to synaptic specificity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS046747-02
Application #
6755055
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Leblanc, Gabrielle G
Project Start
2003-07-01
Project End
2007-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
2
Fiscal Year
2004
Total Cost
$403,427
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
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He, Haihuai; Kise, Yoshiaki; Izadifar, Azadeh et al. (2014) Cell-intrinsic requirement of Dscam1 isoform diversity for axon collateral formation. Science 344:1182-6
Hughes, Michael E; Bortnick, Rachel; Tsubouchi, Asako et al. (2007) Homophilic Dscam interactions control complex dendrite morphogenesis. Neuron 54:417-27
Chen, Brian E; Kondo, Masahiro; Garnier, Amelie et al. (2006) The molecular diversity of Dscam is functionally required for neuronal wiring specificity in Drosophila. Cell 125:607-20
Watson, Fiona L; Puttmann-Holgado, Roland; Thomas, Franziska et al. (2005) Extensive diversity of Ig-superfamily proteins in the immune system of insects. Science 309:1874-8