Anterior-posterior axis formation in the Drosophila oocyte requires activation of the EGF receptor (EGFR) pathway in the posterior follicle cells (PFC), where it also redirects them from the default anterior to the posterior cell fate. The relationship between EGFR activity in the PFC and oocyte polarity is unclear, because no EGFR-induced changes in the PFC have been observed that subsequently affect oocyte polarity. Here, we show that an extracellular matrix receptor, Dystroglycan, is down-regulated in the PFC by EGFR signaling, and this down-regulation is necessary for proper localization of posterior polarity determinants in the oocyte. Failure to down-regulate Dystroglycan disrupts apicobasal polarity in the PFC, which includes mislocalization of the extracellular matrix component Laminin. Our data indicate that Dystroglycan links EGFR-induced repression of the anterior follicle cell fate and anterior-posterior polarity formation in the oocyte.axis specification ͉ gurken ͉ intercellular communication ͉ microtubules ͉ oogenesis F ormation of the main body axes is a critical stage in the development of most multicellular organisms. In Drosophila melanogaster, the main body axes are determined by the polarization of the developing oocyte. Each oocyte develops in the posterior region of an individual egg chamber, which is comprised of the oocyte, 15 germ-line nurse cells, and a surrounding monolayer of somatic follicle cells. The anterior-posterior (AP) body axis is established during stages 9-10 of oogenesis by the microtubuledependent localization of bicoid (bcd) and oskar (osk) RNAs to the anterior and posterior ends of the developing oocyte, respectively (1-4). Formation of the correct microtubule arrangement and AP polarity requires activation of the EGF receptor (EGFR) signaling pathway in the follicle cells directly contacting the oocyte at the posterior of the egg chamber, causing these cells to differentiate as posterior follicle cells (PFCs). EGFR [Torpedo (Top) in Drosophila] is activated in the PFC in early oogenesis by secretion of Gurken (Grk; a TGF-␣ homologue) from the adjacent oocyte. Previous studies have demonstrated that EGFR activation in the PFC cues a complete reorganization of the oocyte microtubule cytoskeleton, such that by stage 9, there is a distinct accumulation of microtubule plus ends in a well defined compartment at the posterior cortex of the oocyte, and the minus ends appear to be concentrated predominately at the anterior region of the oocyte, with some extending along the lateral cortex (3-5). It is this microtubule polarity within the oocyte that serves as the basis for the localization of the RNAs and associated proteins that define the AP axis. Mutations inhibiting EGFR activation in the PFCs preclude this microtubule reorganization and, thus, axis formation. In these cases, osk RNA is mislocalized to the center of the oocyte, and bcd RNA accumulates at both poles of the oocyte (1, 2).Mutations disrupting EGFR activation also inhibit differentiation of the follicle cells c...