Our long-term objective is to understand how genes control the specialization of body segments in Drosophila. Much of our work is focused on the homeotic gene spineless (ss), which specifies the identity of the distal antenna, ss encodes a bHLH PAS transcription factor that is the closest known homolog of the mammalian aryl hydrocarbon receptor (Ahr). Our major objectives are to determine how antennal expression of ss is regulated and how ss controls its downstream targets. Interactions of the upstream regulators Dll, Hth, and Exd with a 521 bp antennal enhancer from ss will be characterized in detail. Interactions between Ss, Hth, Dll, and Exd with three enhancers likely controlled by Ss will also be characterized. Two likely Ss targets identified encode antenna-specific detoxification genes; if these prove to be direct targets of Ss, we will test whether Ahr controls expression of similar genes known to be expressed in the mammalian olfactory system. Our second major focus is on how adult abdominal segments are patterned. We have shown that mutations in the ecdysone-inducible gene E93 cause defects in numerous patterning events in the early pupa, including the patterning of the abdominal tergites. In normal development, many target genes appear to change their responses to EGFR, Hh, and Dpp signaling in the early pupal period; E93 may be at least partly responsible for directing this transition. Our specific goals are to identify products of E93 that function in imaginal patterning, determine the extent to which the early pupal transition is affected by E93, and identify targets of E93 involved in patterning. We also plan to characterize three novel genes that regulate pigmentation in the abdomen; these genes will be mapped and their relationships determined to omb and bob, key pigmentation regulators identified in previous work. Our work will provide insights into the functioning of Ahr, and may lead to a better understanding of how target gene specificity is controlled for signaling systems known to play an important role in cancer.
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