Opposing Regulation of Cell Cluster Movement by Fasciclin II via Neoplastic Tumor Suppressors and a Drosophila AIB1 Negative Feedback Loop. S.A. Goode 1,2,3,4, P. Szafranski 1. 1) Pathology, Baylor Col Medicine, Houston, TX; 2) Program in Developmental Biology; 3) Department of Molecular and Human Genetics; 4) Department of Molecular and Cellular Biology.
Little is known about signal-adhesion pathways governing cell cluster movement. We find that in the Drosophila border cell clusters, polar cells at the center of the cluster express predominantly epithelial lateral proteins. Fasciclin II (FasII) is restricted to polar cells, while neoplastic tumor suppressors Discslarge (Dlg) and Lethal giant larvae (Lgl) are also in border cell cortices. FasII, Dlg, and Lgl utilize the lateral membrane to become localized in PCs in a radial, front-to-back pattern during border cell differentiation and govern expression and localization of specific signaling, adhesion, vesicle, and cytoskeletal proteins in distinct regions of the cluster. Disruption of FasII polarity dramatically delays initiation. FasII has an opposing role in suppressing movement by maintaining Dlg and Lgl in border cells. FasII, Dlg, and Lgl are required for expression or transcriptional coactivator Drosophila Amplified in Breast Cancer-1 (DAIB1) in BCs, while DAIB1 negatively regulates FasII expression and localization, thus forming a negative feedback loop. fasII, dlg, and lgl border cells bypass the normal requirement for DAIB1 in cluster movement.