The Hedgehog (Hh) and Epidermal growth factor receptor (EGFR) signaling pathways play critical roles in pattern formation and cell proliferation in invertebrates and vertebrates. In this study, we demonstrate a direct link

Communication among cells within a developmental field is mediated through signal transduction pathways. Although individual signaling cascades have been studied in detail, the mechanisms through which they interact remain poorly understood. Such interactions can occur between pathways that act either sequentially or in parallel. In the first case, the signal received by a cell through a particular cascade activates or blocks signaling by a downstream pathway. In the case of parallel signaling, two pathways can interact directly, or converge at the level of common signal transducers. One of the most important pathways controlling development is triggered by the Hh protein. Hh mediates both shortand long-range signaling, and is capable in specific tissues of activating the TGFβ, Wnt and FGF pathways (reviewed in Ingham, 1995; Perrimon, 1995; Altaba, 1997). In both invertebrates and vertebrates, the multiple functions of Hh signaling are reflected in the tissue-specific patterns in which hh and hh-related genes are expressed. A second critical developmental signal is transduced through the EGFR. The EGFR is a member of the erbB family of tyrosine kinase receptors, which control both cell proliferation and cell fate. Signals transmitted through the Drosophila EGFR (DER) specify both axes of the oocyte and are required for the development of the embryonic ventral midline, the adult eye and wing, and other tissues (reviewed in Freeman, 1997; Perrimon and Perkins, 1997; Schweitzer and Shilo, 1997). Recent studies have shown that the EGFR cascade interacts with both the Wg and Decapentaplegic (Dpp) pathways in Drosophila. During embryogenesis, competition between EGFR and Wg signaling determines cell fate within the ventral epidermis (O’Keefe et al., 1997; Szuts et al., 1997), while the EGFR and Dpp pathways interact during endoderm specification (Szuts et al., 1998) and tracheal development (Wappner et al., 1997). The DER protein has three known activating ligands. The first is Gurken, which functions only in the germline (Neuman-Silberberg and Schupbach, 1993). The second is Spitz, which is ubiquitously expressed but must be processed to be active (Rutledge et al., 1992; Freeman, 1994; Schweitzer et al., 1995; Golembo et al., 1996b; Gabay et al., 1997). The third ligand, Vn, is a secreted neuregulin-like molecule expressed in a tissue-specific fashion during embryonic and imaginal development (Schnepp et al., 1996; Simcox et al., 1996; Simcox, 1997; Yarnitzky et al., 1997; Szuts et al., 1998). In this study, we demonstrate that Hh induces EGFR signaling during Drosophila head development. We show that eliminating vn expression deletes a subset of the dorsal head structures dependent on Hh for their formation. We also demonstrate that Hh induces vn expression within the imaginal primordium of the dorsal head and analyze the role of the transcription factor Ci in vn induction. Finally, we show that 2623 Development 126, 2623-2630 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 DEV8569