Parallel imaging of Drosophila embryos for quantitative analysis of genetic perturbations of the Ras pathway

Disease Models & Mechanisms
Yogesh GoyalHang Lu

Abstract

The Ras pathway patterns the poles of the Drosophila embryo by downregulating the levels and activity of a DNA-binding transcriptional repressor Capicua (Cic). We demonstrate that the spatiotemporal pattern of Cic during this signaling event can be harnessed for functional studies of mutations in the Ras pathway in human diseases. Our approach relies on a new microfluidic device that enables parallel imaging of Cic dynamics in dozens of live embryos. We found that although the pattern of Cic in early embryos is complex, it can be accurately approximated by a product of one spatial profile and one time-dependent amplitude. Analysis of these functions of space and time alone reveals the differential effects of mutations within the Ras pathway. Given the highly conserved nature of Ras-dependent control of Cic, our approach provides new opportunities for functional analysis of multiple sequence variants from developmental abnormalities and cancers.

References

Nov 24, 1998·Trends in Genetics : TIG·P W Sternberg, M Han
Oct 24, 2002·Brain Research. Molecular Brain Research·Ching-Jung LeePaul J Scotting
May 3, 2003·The EMBO Journal·Marc Furriols, Jordi Casanova
Dec 28, 2010·Nature Methods·Kwanghun ChungHang Lu
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Apr 25, 2012·Journal of Cell Science·Gerardo JiménezZe'ev Paroush
Jul 4, 2012·Briefings in Functional Genomics·Jennifer L Bromberg-WhiteNicholas S Duesbery
Mar 16, 2013·Nature Protocols·Thomas J LevarioHang Lu
Jun 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Bomyi LimStanislav Y Shvartsman
Jul 24, 2013·Annual Review of Genomics and Human Genetics·Katherine A Rauen
Nov 10, 2013·Current Biology : CB·Alan S FutranStanislav Y Shvartsman
Jul 24, 2015·Disease Models & Mechanisms·Granton A JindalStanislav Y Shvartsman
Mar 2, 2016·Annual Review of Biomedical Engineering·Thomas J LevarioHang Lu
Nov 22, 2016·Nature Genetics·Ross A OkimotoTrever G Bivona
Jan 5, 2017·Proceedings of the National Academy of Sciences of the United States of America·Granton A JindalStanislav Y Shvartsman
Jan 25, 2017·Developmental Cell·Heath E JohnsonJared E Toettcher
Feb 7, 2017·Nature Genetics·Yogesh GoyalStanislav Y Shvartsman
Feb 9, 2017·Genes & Development·Sida LiaoStephen J Elledge

❮ Previous
Next ❯

Citations

Oct 12, 2017·The Journal of Biological Chemistry·Granton A JindalStanislav Y Shvartsman
Jan 9, 2020·Molecular Biology of the Cell·Sayantanee PaulAlexey Veraksa
May 3, 2019·Journal of Biological Engineering·Qinfeng WuJeremiah J Zartman
Jan 23, 2020·Integrative Biology : Quantitative Biosciences From Nano to Macro·Alireza ZabihihesariPouya Rezai
Jan 22, 2021·Molecular Biology of the Cell·Robert A MarmionStanislav Y Shvartsman

❮ Previous
Next ❯

Methods Mentioned

BETA
chip

Software Mentioned

MATLAB
COMSOL Multiphysics
ImageJ
AutoDesk

Related Concepts

Related Feeds

Cancer Sequencing

Several sequencing approaches are employed to understand and examine tumor development and progression. These include whole genome as well as RNA sequencing. Here is the latest research on cancer sequencing.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Bomyi LimStanislav Y Shvartsman
Methods in Molecular Biology
Eric M WaltersMatthew B Wheeler
© 2022 Meta ULC. All rights reserved