Drosophila embryonic dorsal-ventral polarity originates in the ovarian follicle through the restriction of pipe gene expression to a ventral subpopulation of follicle cells. Pipe, a homolog of vertebrate glycosaminoglycan-modifying enzymes, directs the ventral activation of an extracellular serine proteolytic cascade

Pattern formation along the dorsal-ventral axis of the developing Drosophila embryo depends upon two sequentially acting signal transduction cascades functioning in the ovarian egg chamber and in the egg, respectively (Ray and Schüpbach, 1996; Morisato and Anderson, 1995). In the egg chamber, spatially restricted activation of the Drosophila EGF receptor homolog, Torpedo, leads to the establishment of dorsal cell fate in the follicle cells in which Torpedo is activated. The spatially restricted activation of Torpedo (Top; Egrf – FlyBase) is mediated by the TGFα homolog, Gurken (Grk), whose mRNA is associated with the oocyte nucleus which is asymmetrically positioned along the DV circumference of the oocyte (Neumann-Silberberg and Schüpbach, 1993). Thus, the position of the oocyte nucleus defines the dorsal side of the egg chamber and only the follicle cells overlying the nucleus receive the signal to assume a dorsal fate. In females carrying loss of function mutations in torpedo (top), gurken (grk), or other members of the receptor signal transduction pathway acting downstream of Top, the egg chambers, eggs and embryos are ventralized, owing to the failure of any follicle cells to assume a dorsal fate (Schüpbach, 1987; Ray and Schüpbach, 1996). The establishment of dorsal-ventral polarity in the embryo depends upon the prior establishment of polarity in the egg chamber. A key event in the establishment of embryonic polarity is the ventrally restricted activation of the uniformly distributed Toll receptor protein (Toll) whose putative ligandbinding domain extends into the perivitelline space lying between the egg shell and the embryonic membrane (Hashimoto et al., 1988). Spatial restriction of Toll activation is thought to result from ventrally restricted processing of a precursor form of the putative Toll ligand, encoded by the spätzle locus (Morisato and Anderson, 1994). Spatially restricted processing of Spätzle occurs via the action of a proteolytic cascade comprising the products of the genes gastrulation-defective (gd), snake and easter, with the activation of the cascade taking place only ventrally in the perivitelline space, thereby restricting the formation of active Toll ligand to the ventral side of the embryo (Morisato and Anderson, 1995). We recently identified the pipe (pip – FlyBase) gene as providing the link between ovarian and embryonic dorsal ventral polarity (Sen et al., 1998). pipe is expressed in the ventral follicle cells under the transcriptional control of the Grk/Top signal transduction pathway. Moreover, this spatial restriction of pipe expression determines the ultimate polarity of the progeny embryo. pipe encodes an enzyme with structural similarity to the vertebrate glycosaminoglycan-modifying enzyme, heparan sulfate 2-O-sulfotransferase (Kobayashi et al., 1997), which led us to propose that spatially restricted 5541 Development 127, 5541-5550 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV5408