The function of the visual system is to form images. As correct patterning of photoreceptor neurons in the retina is critical for the precise retinotopic axonal projections onto the optic lobes, precise photoreceptor arrangement within the retinal epithelium is important. The Drosophila retina is a stereo-typed pattern of several hundred ommatidia, or unit eyes, and the associated photoreceptor neurons. The establishment of this precise arrangement serves as a paradigm for neuronal photoreceptor cell fate induction and patterning. This process requires first sequential waves of EGF-receptor (Egfr)/Ras-signaling activation to induce the respective neuronal fates, simultaneously with Frizzled (Fz)/planar polarity signaling to pattern the photoreceptor neuron clusters correctly. An interesting aspect of the final photoreceptor patterning and arrangement is governed by a process called ommatidial rotation. Fz signaling regulates the direction of rotation during eye development, but a distinct mechanism/pathway is required for the actual execution of the rotation. We have identified the Egfr pathway as critical for the rotation process per se. Interestingly, the downstream effector cascade is distinct from the one used by Egfr for photoreceptor neuron induction and survival. The scope of this application is to dissect the specific Egfr signaling requirements for photoreceptor motility and ommatidial rotation, and to identify the specific effector cascade(s) required downstream of Egfr and Ras in this context. A set of newly identified rotation specific genes will be integrated with the rotation specific Egfr signaling aspects. A combination of Drosophila in vivo studies and biochemical experiments will be used to achieve this goal. Several effectors of Egfr have been identified genetically or molecularly and will be analyzed for their role in ommatidial rotation. Egfr/Ras signaling has also been implicated in many forms of cancer and several of its signaling components (e.g. the receptor and Ras themselves) are proto-oncogenes. Thus, the information acquired in this application will both advance our understanding of retinal cell motility and patterning, and will also be of importance for the study of carcinogenesis. ? ?
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