[Disease Mmodels and Mechanisms] Parallel imaging of Drosophila embryos for quantitative analysis of
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 the Ras-pathway mutations from 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 opens a new way for functional analysis of multiple sequence variants from developmental abnormalities and cancers.
Yogesh Goyal, Thomas J. Levario, Henry H. Mattingly, Susan Holmes, Stanislav Y. Shvartsman, Hang Lu Disease Models & Mechanisms 2017 : doi: 10.1242/dmm.030163