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Drosophila axis detemination; dorsal/ventral polarity How are the embryonic axes set up? How does the embryonic dorsal-ventral axis get translated into differentiation of different tissue types? wildtype Wieschaus and Nüsslein-Volhard looked for mutants that affect the fly body plan Screen for developmental mutants (Drosophila) Lethal hits = 100% (essential genes - ca. 5.000) (efficiency of mutagenesis = number of hits per gene) zygotic mutants embryonal-lethal mutants with morphological defects - segmentation defects (AP) - tissue types defective (DV) female-sterile mutants with effects on embryogenesis (= maternal-effect mutants) - antero-posterior pattern - dorso-ventral pattern 100 % 25 % 3% 0.5 % 0.5 % 8% 2% 0.4 % 0.3 % (male-sterile mutants) ca. 2% of all genes involved in embryo pattern formation (ca. 100 of >15.000 protein-encoding genes, only 5.000 essential genes) Maternal-effect mutations Genes expressed during oogenesis (= before fertilization) All progeny of heterozygous mother normal All progeny affected only if mother homozygous mutant Zygotic mutations Genes expressed during embryogenesis (= after fertilization) Only genetically mutant embryos affected (25% of progeny of heterozygous mother) Genes identified in a famous screen for Drosophila mutants with embryo patterning defects Gurken protein specifies the Anterior-Posterior axis of the Drosophila embryo during oogenesis (Similar to EGF) Localized maternal mRNA sets up anterior and posterior poles Gurken also signals dorsal pole formation during oogenesis oocyte nucleus 1-6 A + 7 8 D migration of nucleus 10A D - P anterior posterior V V follicle cells microtubules 8 10A 1-6 + gurken expression in the oocyte gurken expression in the oocyte Expression of the Gurken Message and Protein Between the Oocyte Nucleus and the Dorsal Anterior Cell Membrane DORSO-VENTRAL PATTERN FORMATION follicle cells Torpedo = EGF receptor (in follicle cells) Gurken = Epidermal Growth Factor (EGF) Oocyte pipe expression X Ventral follicle cell Pipe (Golgi?) X Wind (ER?) Nucleus X mod. from van Eeden & St.Johnston Genes identified in a famous screen for Drosophila mutants with embryo patterning defects Torpedo Dorsal-Ventral fate map Cell fate specification at the blastoderm stage amnioserosa dorsal dorsal ectoderm neuroectoderm mesoderm ventral fate map mesoderm formation Dorso-ventral pattern formation Maternal effect mutations nudel, pipe, wbl ndl, pipe, wbl gd, snk, ea - serine proteases dorsal RNA spz - ligand Toll protein Spätzle protein Toll Tl - membrane receptor Dorsal protein Zygotic mutations Dorsal protein tube - cytoplasmic protein pelle - ser/thr protein kinase cactus amnio serosa cact - cytoplasmic inhibitor dorsal ectoderm of Dorsal nuclear translocation dorsal neuroectoderm dl - transcription factor (morphogen) mesoderm Dl nuclear protein Dorso-ventral pattern formation dorsal Wild type dorsal cactus mutant mutant A7 A8 A6 A5 A4 A3 A2 T3 A1 T2 T1 ventral dorsalized ventralized Translocation of Dorsal protein into ventral nuclei but not lateral or dorsal nuclei Wild type toll mutant cactus mutant Generation of Dorsal-Ventral Polarity in Drosophila Generation of Dorsal-Ventral Polarity in Drosophila Dorso-ventral pattern formation pivotal role of Toll pathway Inject wild-type cytoplasm into toll mutant eggs toll mutant ventral dorsalized local rescue Wild type dorsal ectoderm dorsal neuro-ectoderm (denticle belts) mesoderm polarity reversal Conserved pathway for regulating nuclear transport of transcription factors in Drosophila and mammals Action of Dorsal protein in ventral cells Action of Dorsal protein in ventral cells High affinity for promoter, Not much Dorsal needed to activate Action of Dorsal protein in ventral cells Lower affinity for promoter, More Dorsal needed to activate Dorso-ventral pattern formation: summary nudel, pipe, windbeutel dorsal RNA Toll protein Spätzle protein Dorsal protein Dorsal protein dpp twist oocyte nucleus dorsal > repression of ventral fate in dorsal follicle cells ventral production of ligand > activation of Toll receptor > graded nuclear uptake of Dorsal morphogen > regulation of zygotic target gene expression > cell fates along DV axis Gastrulation in Drosophila Schematic representation of gastrulation in Drosophila Use of a similar regulatory system to pattern insects and vertebrates Patterns ectoderm in Drosophila Patterns mesoderm in vertebrates Anterior-posterior patterning in Drosophila Maternal effect mutations Zygotic effect mutations (receptor) (required to produce ligand from Trunk)
