INHIBITION OF PATTERNED CELL-SHAPE CHANGE AND CELL INVASION BY DISCS LARGE DURING DROSOPHILA OOGENESIS

Drosophila Discs large (Dig) is a tumor suppressor gene whose loss in epithelial tissues causes disrupted cell polarity and increased cell p roliferation. A human Dig homolog, hDlg, has been implicated in tumori genic processes via its association with the product of the Adenomatou s polyposis Coli (APC) gene. We show for the first time that Drosophil a Dig is required to block cell invasion. Loss of dig activity during oogenesis causes follicle cells to change shape and invade in a patter n similar to border cells, a small population of cells that break from the post-mitotic follicular epithelium during wild-type oogenesis, ye t dig mutant cells have not adopted a border cell fate. Both functiona l and morphological evidence indicates that cooperation between germ c ell and follicle cell Dlg, probably mediated by Dlg PDZ domains, is cr ucial for regulating cell mixing, suggesting a novel developmental mec hanism and mode of action for the Dig family of molecules. These findi ngs suggest that Dlg does not simply inhibit individual cell behaviors during oogenesis, but rather acts in a developmental pathway essentia l for blocking cell proliferation and migration in a spatio-temporally defined manner. A model for Dlg action in blocking cell invasion is p resented.