INTRODUCTION Patterning the follicle cells that cover the developing oocyte determines the polarity of the Drosophila embryo. This is achieved by an elaborate communication between the oocyte and the surrounding follicle cells. Eventually, signals from the follicle cells determine the polarity of the future embryonic axes. The specification of at least three subsets of follicle cells, posterior, dorsal and terminal, is responsible for determining the anterioposterior and dorsoventral axes of the embryo, and the terminal structures, respectively (reviewed by Ray and Schüpbach, 1996). Surprisingly, the pathway triggered by the Drosophila EGF receptor (DER/Torpedo/EGFR) is responsible for the determination of both posterior and dorsal follicle cell fates, at two discrete stages of oogenesis (González-Reyes et al., 1995; Roth et al., 1995; Price et al., 1989). The anterioposterior axis is the first to be specified in the developing oocyte. From the initial stages of oogenesis, the population of follicle cells covering the oocyte is not uniform. Situated at both termini is a small group of polar follicle cells that has been determined at an earlier stage (Ruohola et al., 1991; Margolis and Spradling, 1995). There appears to be no distinction at this phase however, between the anterior and posterior follicle cells. Prior to stage 7, gurken transcripts, encoding a TGFα homologue that is likely to be a ligand for DER, are localized at the space between the oocyte nucleus and the posterior part of the oocyte (Neuman-Silberberg and Schüpbach, 1993). DER, in contrast, is expressed in all follicle cells (described below). Activation of DER by Gurken at the posterior follicle cells induces posterior follicle cell fates, which are distinct from the default fate that is maintained in the anterior follicle cells. The posterior cells then signal back to the oocyte, through an unknown mechanism. Consequently, reorganization of the microtubule and microfilament system of the oocyte ensues, and the localization of mRNAs (e.g. bicoid and oskar) along the anterioposterior axis takes place. This system is also responsible for directing migration of the oocyte nucleus to an anterior peripheral position in the oocyte, which will subsequently become the dorsal region. Migration of the oocyte nucleus is completed by stage 8-9. In parallel to the continuous growth of the oocyte, posterior migration of follicle cells over the oocyte is observed. By stage 10 the nurse cells, which occupy half of the egg chamber, are covered by only approx. 50 thin follicle cells (the stretch cells), while the oocyte itself is surrounded by the remaining approx. 1,000 follicle cells, which are columnar in shape (reviewed by Spradling, 1993). gurken transcripts maintain their close association with the migrating oocyte nucleus (Neuman-Silberberg and Schüpbach, 1993). After completion of nuclear migration, a second phase of DER activation takes place, this time leading to the induction of dorsal follicle cell fates. The dorsal-anterior cells 191 Development 125, 191-200 (1998) Printed in Great Britain © The Company of Biologists Limited 1998 DEV7613 Previous work has demonstrated a role for the Drosophila EGF receptor (Torpedo/DER) and its ligand, Gurken, in the determination of anterioposterior and dorsoventral axes of the follicle cells and oocyte. The roles of DER in establishing the polarity of the follicle cells were examined further, by following the expression of DER-target genes. One class of genes (e.g. kekon) is induced by the DER pathway at all stages. Broad expression of kekon at the stage in which the follicle cells migrate posteriorly over the oocyte, demonstrates the capacity of the pathway to pattern all follicle cells except the ventral-most rows. This may provide the spatial coordinates for the ventral-most follicle cell fates. A second group of target genes (e.g. rhomboid (rho)) is induced only at later stages of oogenesis, and may require additional inputs by signals emanating from the anterior, stretch follicle cells. The function of Rho was analyzed by ectopic expression in the stretch follicle cells, and shown to induce a non-autonomous dorsalizing activity that is independent of Gurken. Rho thus appears to be involved in processing a DER ligand in the follicle cells, to pattern the egg chamber and allow persistent activation of the DER pathway during formation of the dorsal appendages. Key words: EGF receptor, Oogenesis, Rhomboid, Gurken, Drosophila SUMMARY Sequential activation of the EGF receptor pathway during Drosophila oogenesis establishes the dorsoventral axis Amir Sapir*, Ronen Schweitzer* ,† and Ben-Zion Shilo ‡ Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel *These two authors contributed equally to the work † Present address: Department of Genetics, Harvard Medical School, Boston MA 02115, USA ‡ Author for correspondence (e mail: lvshilo@weizmann.weizmann.ac.il) Accepted 10 November 1997: published on WWW 17 December 1997