The product of the Drosophila easter gene, a member of the trypsin family of serine proteases, must be more active ventrally than dorsally to promote normal embryonic polarity. The majority of the Easter protein in the embryo is present in the unprocessed zymogen form and appears to be evenly distributed in the extracellular space, indicating that the asymmetric activity of wild-type Easter must arise post-translationally. A dominant mutant form of easter that does not require cleavage of the zymogen for activity is active both dorsally and ventrally. The dominant mutant bypasses the requirement for five other maternal effect genes, indicating that these five genes exert their effects on dorsal-ventral patterning solely by controlling the activation of the Easter zymogen (Chasan, 1992).

Effects of Mutation or Deletion

The embryonic phenotypes produced by many of the eaD mutations have been described at the level of cuticle patterns and gastrulation behavior (Chasan, 1989; Jin, 1990). Focus was placed on five alleles that are classified as being ventralized (ea125.3, ea83l and ea5022) or lateralized (ea20n and ea5.13). These alleles are completely penetrant and show a spectrum of phenotypes, in contrast to the dorsalization caused by a loss of maternal easter function. Each eaD mutation is caused by a single amino acid substitution in a conserved region of the Easter catalytic domain (Jin, 1990; Chang, 2002).

Among the ventralizing alleles, embryos produced by ea125.3/+ females exhibit the weakest effects, with only slight expansion of ventral denticle bands (Chasan, 1989). Embryos laid by ea83l/+ and ea5022/+ females showed stronger phenotypes, characterized by the expansion of ventral denticle bands, reduction or absence of dorsolaterally derived structures, such as the filzkörper, and near absence of dorsal hairs (Chasan, 1989). Embryos laid by ea5022/+ females exhibit more disorganized denticles and more severe head deformities than embryos laid by ea83l/+ females. At gastrulation, embryos produced by females carrying all three alleles invaginated an apparently normal ventral furrow, but initiation of the lateral cephalic furrow is shifted to a more dorsal position and fewer dorsal folds are formed (Chang, 2002).

Embryos produced by females carrying the lateralizing alleles ea20n and ea5.13 show a marked reduction in dorsoventral asymmetry. Unlike the other eaD alleles, ea20n/+ females lay a mixture of ventralized and lateralized embryos, as determined by analyzing both differentiated cuticles and gastrulation movements. The ventralized embryos show a stronger phenotype than do embryos laid by ea83l/+ and ea5022/+ females. By comparison, all of the embryos laid by ea5.13/+ females show a reduction in both dorsal pattern elements and ventrally derived mesoderm, developing a cuticle with rings of ventral and lateral denticle bands (Chasan, 1989). At gastrulation, embryos from ea5.13/+ females fail to invaginate a ventral furrow and exhibit a widened head fold (Chang, 2002).

The phenotypes of embryos produced by eaD females were examined in the absence of wild-type maternal easter activity, in order to study the genetic dominance exerted by these eaD mutations. For the ventralizing alleles, embryos produced by eaD/+ and eaD/ea- females are virtually indistinguishable. By contrast, the embryos produced by ea20n/ea- and ea5.13/ea- females are markedly more elongated and have fewer ventral denticle bands than embryos laid by ea20n/+ and ea5.13/+ females. Notably, all the embryos laid by ea20n/ea- females develop a lateralized head fold during gastrulation, when compared with the mixed population laid by ea20n/+ females. In summary, the presence of a wild-type dose of easter is able to confer detectable dorsoventral asymmetry to embryos produced by the lateralizing eaD alleles (Chang, 2002).

Taken together, the analysis of gastrulation behavior and differentiated cuticles suggests that the five eaD mutations can be ordered in the following allelic series, with the strongest allele exhibiting the greatest loss of dorsoventral polarity: wild type>ea125.3>ea83l>ea5022>ea20n>ea5.13 (Chang, 2002).

The primary interest in the eaD mutations is to understand their effects on the Dorsal gradient. Although embryos could be stained directly for the expression of Dorsal protein, it was felt that changes in the shape of the gradient would be too subtle to discern and difficult to quantitate. Therefore, the expression domains were characterized of the zygotic genes zen, sog, rho and twist, each corresponding to a specific concentration range of nuclear Dorsal. In order to simplify comparisons between embryos, domain size was expressed as a percentage of the embryo circumference. The major points from these data are summarized below (Chang, 2002).


Chang, A. J. and Morisato, D. (2002). Regulation of Easter activity is required for shaping the Dorsal gradient in the Drosophila embryo Development 129: 5635-5645. 12421704

Chasan, R. and Anderson, K. V. (1989). The role of Easter, an apparent serine protease, in organizing the dorsal-ventral pattern of the Drosophila embryo. Cell 56: 391-400. 2492450

Chasen, R., Jin, Y. and Anderson, K. V. (1992). Activation of the easter zymogen is regulated by five other genes to define dorsal-ventral polarity in the Drosophila embryo. Development 115: 607-16.

Dissing, M., Giordano, H. and DeLotto, R. (2001). Autoproteolysis and feedback in a protease cascade directing Drosophila dorsal-ventral cell fate. EMBO J. 20: 2387-2393. 11350927

Gay, N. J. and Keith, F. J. (1992). Regulation of translation and proteolysis during the development of embryonic dorso-ventral polarity in Drosophila. Homology of easter proteinase with Limulus proclotting enzyme and translational activation of Toll receptor synthesis. Biochim. Biophys. Acta 1132: 290-6.

Hashimoto, C., et al. (2003). Spatial regulation of developmental signaling by a serpin. Dev. Cell 5: 945-950. 14667416

Jin, Y. S. and Anderson, K. V. (1990). Dominant and recessive alleles of the Drosophila easter gene are point mutations at conserved sites in the serine protease catalytic domain. Cell 60: 873-81.

Konrad, K. D., et al. (1998). The gastrulation defective gene of Drosophila melanogaster is a member of the serine protease superfamily. Proc. Natl. Acad. Sci. 95(12): 6819-6824.

LeMosy, E. K., Tan, Y.-Q. and Hashimoto, C. (2001). Activation of a protease cascade involved in patterning the Drosophila embryo. Proc. Natl. Acad. Sci. 98: 5055-5060. 11296245

LeMosy, E. K., et al. (2006). Spatially dependent activation of the patterning protease, Easter. FEBS Letters 580: 2269-2272. 16566925

Ligoxygakis, P., Roth, S. and Reichhart, J.-M. (2003). A serpin regulates dorsal-ventral axis formation in the Drosophila embryo. Curr. Biol. 13: 2097-2102. 14654000

Ligoxygakis, P., Roth, S. and Reichhart, J.-M. (2003). A serpin regulates dorsal-ventral axis formation in the Drosophila embryo. Curr. Biol. 13: 2097-2102. 14654000

Misra, S., Hecht, P., Maeda, R. and Anderson, K.V. (1998). Positive and negative regulation of Easter, a member of the serine protease family that controls dorsal-ventral patterning in the Drosophila embryo. Development 125: 1261-1267. 9477324

Schneider, D. S., Jin, Y., Morisato, D. and Anderson, K. V. (1994). A processed form of the SpƤtzle protein defines dorsal-ventral polarity in the Drosophila embryo. Development 120: 1243-1250. 8026333

Smith, C. L., Giordano, H. and DeLotto, R. (1994). Mutational analysis of the Drosophila snake protease: an essential role for domains within the proenzyme polypeptide chain. Genetics 136: 1355-65.

Stein, D., Roth, S., Vogelsang, E. and Nüsslein-Volhard, C. (1991). The polarity of the dorsoventral axis in the Drosophila embryo is defined by an extracellular signal. Cell 65: 725-735

Stein, D. and Nüsslein-Volhard, C. (1992). Multiple extracellular activities in Drosophila egg perivitelline fluid are required for establishment of embryonic dorsal-ventral polarity. Cell 68: 429-440. 1739964

Steward, R. (1989). Relocalization of the Dorsal protein from the cytoplasm to the nucleus correlates with its function. Cell 59: 1179-1188. 2598266

easter: Biological Overview | Regulation | Developmental Biology | Effects of Mutation

date revised: 20 December 2006

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