A screen for dominant mutations applied to components in the Drosophila EGF-R pathway

Proceedings of the National Academy of Sciences of the United States of America
Annabel GuichardEthan Bier

Abstract

The Drosophila epidermal growth factor receptor (EGF-R) controls many critical cell fate choices throughout development. Several proteins collaborate to promote localized EGF-R activation, such as Star and Rhomboid (Rho), which act sequentially to ensure the maturation and processing of inactive membrane-bound EGF ligands. To gain insights into the mechanisms underlying Rho and Star function, we developed a mutagenesis scheme to isolate novel overexpression activity (NOVA) alleles. In the case of rho, we isolated a dominant neomorphic allele, which interferes with Notch signaling, as well as a dominant-negative allele, which produces RNA interference-like flip-back transcripts that reduce endogenous rho expression. We also obtained dominant-negative and neomorphic Star mutations, which have phenotypes similar to those of rho NOVA alleles, as well as dominant-negative Egf-r alleles. The isolation of dominant alleles in several different genes suggests that NOVA mutagenesis should be widely applicable and emerge as an effective tool for generating dominant mutations in genes of unknown function.

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Citations

Apr 19, 2008·Cold Spring Harbor Symposia on Quantitative Biology·K FoltenyiR J Greenspan
Oct 8, 2011·Disease Models & Mechanisms·Ethan Bier, Annabel Guichard
Sep 27, 2002·Genesis : the Journal of Genetics and Development·Joseph B Duffy
Jun 21, 2005·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Takatoshi NakagawaRik Derynck
Apr 1, 2021·Disease Models & Mechanisms·Abdul Jalil RufaihahCitra N Z Mattar

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