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, 8 (4), 218-25

Powerful Drosophila Screens That Paved the Wingless Pathway


Powerful Drosophila Screens That Paved the Wingless Pathway

Fabian Heinz Jenny et al. Fly (Austin).


The Wnt/Wingless (Wg) signaling cascade controls a number of biological processes in animal development and adult life; aberrant Wnt/Wg signaling can cause diseases. In the 1980s genes were discovered that encode core Wnt/Wg pathway components: their mutant phenotypes were similar and an outline of a signaling cascade emerged. Over the years our knowledge of this important signaling system increased and more components were uncovered that are instrumental for Wnt/Wg secretion and transduction. Here we provide an overview of these discoveries, the technologies involved, with a particular focus on the important role Drosophila screens played in this process.

Keywords: Drosophila melanogaster; Wg; Wnt; Wnt signaling; development; genetic screens; genetics; wingless signaling; β-catenin.


Figure 1.
Figure 1.
The mechanics and history of Wnt/Wg signaling. (A) The current Wnt/Wg signaling model with its core components and (B) a historic timeline overview regarding the discovery of these signaling components. The color code indicates whether the individual components were discovered in Drosophila, Caenorhabditis elegans or in vertebrates.
Figure 2.
Figure 2.
Genetics of Drosophila screens for Wnt/Wg signaling components. (A) The first patterning screens were performed by Nüsslein-Volhard and Wieschaus. Flies were mutagenized and lines with interesting candidates were established. Here we show the crossing schemes for the isolation of X-linked lethal mutations. (B) Perrimon adapted these first screens for zygotic lethals and removed maternal contributions using the ovoD system, which relies on a female-sterile mutation and mitotic recombination by X irradiation. (C) The Bejsovec lab sensitized the genetic background with a hypomorphic arm allele, which was more susceptible for negative components, such as Pan/Gro and APC2 and (D) the Nusse group identified Axin in a dsh overexpression screen. (E and F) Our lab has carried out suppressor screens using wg mis-expression, induced by the activity of the sev enhancer. (E) A dominant suppressor screen for suppressors of the sev-wg phenotype yielded pan, lgs and pygo. (F) This setting was further developed for recessive suppressor screens based on Flp-induced recombination. In this screen wls was discovered. The remaining chromosome arms are screened with an improved method, where the wg transgene carries a flp-out cassette, which is removed in the eye by ey-Flp (eyeless promoter driven Flipase). The corresponding tester lines carry an FRT site as well as a cell lethal (cl) allele. Marked in red are the mutagenized chromosomes.

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