We propose to study embryogenesis of the nervous system in Drosophila. Techniques employed include genetics and the use of antibodies. Monoclonal antibodies that recognize all, or part of, nervous tissues have been generated and may be useful in two aspects: On the one hand, they serve as markers in studying neural development in normal and mutant animals. On the other hand, they provide a chance for me to get at molecules that are potentially important for development. A major difficulty of the latter approach concerns the question of causality. Even if the antigen recongized by a monoclonal antibody shows an interesting distribution and developmental profile, it is difficult to know whether the antigen itself is developmentally important or whether it is merely a secondary byproduct. This may be resolved if one can show that the monoclonal antibody functionally blocks specific processes during development. Alternatively, if mutations of the structural gene coding for an antigen block specific processes during development, that antigen is probably important developmentally. For genetic studies Drosophila has been a favorable animal. A variety of developmental mutations have been isolated and analyzed. It is possible to use methods such as segmental aneuploidy to localize structrual genes, and to isolate mutations of these genes once they are localized on the salivary chromosome. The wealth of Drosophila genetics may be used to test critically whether a particular gene product is important developmentally. The monoclonal antibodies that we have generated so far subdivide neurons and fiber pathways in various ways and show different developmental profiles. Further, immunohistochemical experiments revealed that the pattern of fiber pathways in the central nervous system of Drosophila embryos appeared very similar to that in grasshopper embryos. To study neurla development in Drosophila embryos, we hope to draw from the rich source of information obtained from studies on grasshoppers. A number of monoclonal antibodies generated so far recognize embryonic nervous tissue in both insects and may serve as a bridge, allowing one to combine Drosophila genetics with advantages of larger insects such as the grasshopper.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019191-03
Application #
3399164
Study Section
Genetics Study Section (GEN)
Project Start
1983-01-01
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Caudy, M; Vassin, H; Brand, M et al. (1988) daughterless, a Drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex. Cell 55:1061-7
Caudy, M; Grell, E H; Dambly-Chaudiere, C et al. (1988) The maternal sex determination gene daughterless has zygotic activity necessary for the formation of peripheral neurons in Drosophila. Genes Dev 2:843-52
Bier, E; Ackerman, L; Barbel, S et al. (1988) Identification and characterization of a neuron-specific nuclear antigen in Drosophila. Science 240:913-6
Bodmer, R; Barbel, S; Sheperd, S et al. (1987) Transformation of sensory organs by mutations of the cut locus of D. melanogaster. Cell 51:293-307
Dambly-Chaudiere, C; Ghysen, A; Jan, Y N et al. (1986) Muscle connections between imaginal discs in Drosophila. Dev Biol 113:288-94
Ghysen, A; Jan, L Y; Jan, Y N (1985) Segmental determination in Drosophila central nervous system. Cell 40:943-8
Jan, Y N; Ghysen, A; Christoph, I et al. (1985) Formation of neuronal pathways in the imaginal discs of Drosophila melanogaster. J Neurosci 5:2453-64