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.
