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Defects in early neurogenic development are associated with a wide range of pathological conditions. The Fred protein, a transmembrane IgC2 protein, is necessary for normal development and critical for the Notch signaling pathway. Using Drosophila melanogaster as the model, the regulatory roles of other genes can be studied that exhibit functional interactions with these genes. Macro- and micro-chaeta sensory bristles (large and small bristles) cover the adult fly and provide an avenue to study cell fate. As each bristle originates from an individual sensory organ precursor cell, the presence or absence of sensory bristles indicates sensory organ precursor cell differentiation. From an RNAi mini screen of an array of candidate genes, 2 genes, cullin-2 (cul-2) and tumbleweed (tum), were identified and exhibited a phenotype similar to that of fred, specifically a loss of function. cul-2 is a scaffold protein for ubiquitin ligase, while tum is involved in GTPase inactivation. An additional aim of this study is to understand how these two genes interact within the fred pathway. The two genes were identified using the inducible RNAi / GAL4/ UAS system. The GAL4/UAS system allows one to induce gene specific RNAi in specific tissues and at defined developmental times. Observing the phenotypical consequences of this down regulation occurs at two levels: (1) the adult animal, and (2) in imaginal wing disc of late 3rd instar larvae. Additional studies have been started to further define the phenotype of these genes and their respective interactions with fred gene function. Initial experimental observations suggest that tum, indeed, may have additional roles in the regulation of muscle attachment sites. Furthermore, double mutations of cul-2 and tum, tum and fred, tum and sc are being analyzed to determine potential epistatic relationships.