The activated Torpedo receptor protein activates Mirror, a transcription factor that represses expression of the pipe gene (Andreu et al. 2012; Fuchs et al. 2012). As a result, Pipe is made only in the ventral follicle cells (Figure 1A; Sen et al. 1998; Amiri and Stein 2002). Pipe protein modifies the ventral vitelline envelope by sulfonating its proteins. This allows the Gastrulation-defective protein to bind to the vitelline envelope (only in the ventral region) and to recruit other proteins to make a complex that will cleave the Easter protein into its active protease form (Figure 1B; Cho et al. 2010, 2012). Easter then cleaves the Spätzle protein (Chasan et al. 1992; Hong and Hashimoto 1995; LeMosy et al. 2001), and the cleaved Spätzle protein is the ligand that binds to and activates the Toll receptor on the membrane of the embryo. It is important that the cleavage of Spätzle be limited to the most ventral portion of the embryo. This is accomplished by the secretion of a protease inhibitor from the follicle cells of the ovary. This can inhibit any small amounts of proteases that might be expected on the margins (Hashimoto et al. 2003; Ligoxygakis et al. 2003).
Toll protein is a maternal product that is evenly distributed throughout the cell membrane of the egg (Hashimoto et al. 1988, 1991), but it becomes activated only by binding Spätzle, which is produced only on the ventral side of the egg. The ventral Toll receptors bind the mature Spätzle protein, and the membrane containing activated Toll protein undergoes endocytosis. Signaling from the Toll receptor is believed to occur in these cytoplasmic endosomes rather than on the cell surface (Lund et al. 2010). Therefore, the Toll receptors on the ventral side of the egg are transducing a signal into the egg, whereas the Toll receptors on the dorsal side are not. This localized activation establishes the dorsal-ventral polarity of the oocyte.
Amiri, A. and D. Stein. 2002. Dorsoventral patterning: A direct route from ovary to embryo. Curr. Biol. 12: R532–R534.
Andreu, M. J., and 6 others. 2012. Mirror represses pipe expression in follicle cells to initiate dorsoventral axis formation in Drosophila. Development 139: 1110–1114.
Chasan, R., Y. Jin and K. V. Anderson. 1992. Activation of the easter zymogen is regulated by five other genes to define dorsal-ventral polarity in the Drosophila embryo. Development 115: 607–615.
Cho, Y. S., L. M. Stevens and D. Stein. 2010. Pipe-dependent ventral processing of Easter by Snake is the defining step in Drosophila embryo DV axis formation. Curr. Biol. 20: 1133–1137.
Cho, Y. S., L. M. Stevens, K. J. Sieverman, J. Nguyen and D. Stein. 2012. A ventrally localized protease in the Drosophila egg controls embryo dorsoventral polarity. Curr. Biol. 22: 1013–1018.
Fuchs, A., L. S. Cheung, E. Charbonnier, S. Y. Shvartsman and G. Pyrowolakis. 2012. Transcriptional interpretation of the EGF receptor signaling gradient. Proc. Natl. Acad. Sci. USA 109: 1572–1577.
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Hashimoto, C., K. L. Hudson and K. V. Anderson. 1988. The Toll gene of Drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein. Cell 52: 269–279.
Hashimoto, C., S. Gerttula and K. V. Anderson. 1991. Plasma membrane localization of the Toll protein in the syncytial Drosophila embryo: Importance of transmembrane signalling for dorsal-ventral pattern formation. Development 11: 1021–1028.
Hong, C. C. and C. Hashimoto. 1995. An unusual mosaic protein with a protease domain, encoded by the nudel gene, is involved in defining embryonic dorsoventral polarity in Drosophila. Cell 82: 785–794.
LeMosy, E. K., Y. Q. Tan and C. Hashimoto. 2001. Activation of a protease cascade involved in patterning the Drosophila embryo. Proc. Natl. Acad. Sci. USA. 98: 5055–5060.
Ligoxygakis, P., S. Roth and J. M. Reichart. 2003. A serpin regulates dorsal-ventral axis formation in the Drosophila embryo. Curr. Biol. 13: 2097–2102.
Lund, V. K., Y. DeLotto and R. DeLotto. 2010. Endocytosis is required for Toll signaling and shaping of the Dorsal/NF-kB morphogen gradient duringDrosophila embryogenesis. Proc. Natl. Acad. Sci. USA 107: 18028–18033.
Sen, J., J. S. Goltz, L. Stevens and D. Stein. 1998. Spatially restricted expression of pipe in the Drosophila egg chamber defines embryonic dorsal-ventral polarity. Cell 95: 471–481.
van Eeden, F. and D. St. Johnston. 1999. The polarisation of the anterior-posterior and dorsal-ventral axes during Drosophila oogenesis. Curr. Opin. Genet. Dev. 9: 396–404.