Drosophila homologs of the human tumor suppressor adenomatous polyposis coli have novel roles in CNS development

Adenomatous Polyposis Coli (APC) is a potent tumor suppressor in humans. Loss of function mutations in APC are found in a large majority of both sporadic and hereditary cases of colon cancer. APC has been shown to have many important cellular functions. It is an important negative regulator of Wnt signaling, a pathway that is important in both normal development and oncogenesis. APC also can associate with the microtubule cytoskeleton and influence its dynamics during important processes such as mitosis. APC is the founding member of a family of proteins. Two family members have been identified in both mammals and insects. The fruitfly Drosophila melanogaster is an ideal model organism in which to further study the roles of APC family members. Fly APC family members participate in regulation of Wg signaling, the highly conserved counterpart of vertebrate Wnt signaling. In addition, fly APCs also associate with the actin and microtubule cytoskeletons, and have been shown to affect their dynamics in certain contexts. Using the powerful genetics of the fruitfly, I have identified novel roles for APC family members during Drosophila development, and gained further insight into how the family members may function together. I have identified contexts in which the two fly APCs, APC1 and APC2, function redundantly in Wg signaling, and other contexts where they function together regulating the cytoskeleton. APC1 and APC2 play partially redundant roles in regulating the Wg pathway in both the embryonic epidermis and in the larval imaginal discs, where Wg signaling is important in establishing patterning of the body plan. Further, I have identified redundant roles for APC1 and APC2 in establishing proper cell and tissue morphology in the developing brain. In this role, APCs may function together to affect important cellular processes such as cell adhesion by influencing the cytoskeleton.