Fibroblast-Growth-Factor (FGF) Pathways. The FGF pathway, which is a subset of the RTK pathways, is not used in either the eye or the wing in Drosophila, but it is required for proper tracheal branching, a process that is readily visible in living larvae by a variety of techniques. Consequently, specific interference with this pathway might also be detectable (Klambt et al. 1992). The tracheae are branched airways of the respiratory system of Drosophila. Their development has interesting similarities to angiogenesis in vertebrates, which involves FGF signaling.

Stress Pathways. Much of the original characterization of these pathways (e.g., the heat-shock response) was done in Drosophila. For convenient scoring of chemical effects, a variety of transgeneic strains have been constructed with reporter genes that are activated under conditions of stress.

Cell-Cycle Control. Drosophila might also be useful for the analysis of compounds that interfere with control of the cell cycle or that activate various checkpoint control pathways. Compounds stored in the egg during oogenesis support nearly all of the critical cell divisions required to achieve the free-living larval stage. During the larval stages, growth of the larva occurs by polyploidization and cell enlargement rather than by cell division. The only dividing cells in the larva are the precursors of the adult structures, and they increase in number prior to metamorphosis in the pupal stage. Most loss-of-function mutations in genes that are required for the cell cycle result in larval lethality, often at the larval and pupal boundary (metamorphosis), when the absence of adult precursor cells becomes critical. Consequently, it should be possible to test various chemicals for their ability to thwart the growth of adult precursor cells.

It could be argued that toxicant effects of the cell cycle are better studied in defined cultured conditions with, for example, culture-adapted differentiated cells. Indeed, cell lines are available, or could be prepared, with one or the other of the 17 intercellular signaling pathways functioning in culture, and these would be valuable for assessments of toxicant effects (e.g., effects on activin’s action as an erythroid differentiation factor in human erythroleukemic cell lines). The advantage of a proliferating developing system, such as the Drosophila imaginal discs described above, is that several signaling pathways simultaneously influence proliferation, in their full complexity of signal release via the Golgi and signal modification in the extracellular space, in addition to signal reception and transduction. Thus, the initial net cast to find toxicant effects might be wider than that in a cell culture system. Still, the latter could be very useful in focused identification and analysis of toxicant effects.

Possible Assays of Behavioral Development in Drosophila

Because of complex courtship behavior, feeding habits, and biological



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