FIGURE 7-5 Effects of peptidomimetics on eye development in Drosophila. (Panel A) Normal compound eye with 800 ommatidia, each a bundle of seven photoreceptor cells and a bristle. (Panel B) The eye of a RAS val12 mutant in which the receptor tyrosine kinase (the sevenless pathway) is overactive. Note the disarrangement of ommatidia. (Panel C) A pupa was injected with a peptidomimetic that blocks isoprenylation, hence interfering with Ras membrane binding and activity. This reduces the activity of the pathway toward normal. The eye is more normal in development. (Kauffmann et al. 1995).

Transforming-Growth-Factor (TGF) β Pathways. The Dpp gene in Drosophila has been instrumental for identifying downstream components of the mammalian TGFβ cascade, such as the SMAD genes (Chanut and Heberlein 1997). Dpp is required in both the eye and the wing for normal development, and there are specific alleles of Dpp that strongly affect each of those organs. In addition, stronger alleles could be used in combination with a clonal analysis.

Hedgehog Pathways. Although Hh functions in the eye, its effect is not easily seen in small clones, presumably because of the diffusible nature of the HH protein (Heberlein et al. 1995). Effects might be more visible in wing clones, or it might be useful to develop sensitized systems for one of the downstream functions of the Hedgehog pathway, such as protein kinase A or the transcription factor cubitus interruptus (equivalent to the GLI oncogene in mammals).

Notch Pathways. Notch is required both for eye development and formation of the sensory components along the wing edge (Baker and Yu 1997). A wide variety of mutations specifically affecting the wing are available; therefore, clonal analysis should be useful.

Wnt Pathways. The Wingless ligand is required for establishing pattern in the wing and legs, and for limiting the eye domain. Clonal analysis of sensitized mutations should be efficient in detecting components of this widely used pathway.



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