Spatiotemporally controlled genetic perturbation for efficient large-scale studies of cell non-autonomous effects

Research output: Contribution to journalArticlepeer-review

133 Downloads (Pure)

Abstract

Studies in genetic model organisms have revealed much about the development and pathology of complex tissues. Most have focused on cell-intrinsic gene functions and mechanisms. Much less is known about how transformed, or otherwise functionally disrupted, cells interact with healthy ones towards a favorable or pathological outcome. This is largely due to technical limitations. We developed new genetic tools in Drosophila melanogaster that permit efficient multiplexed gain- and loss-of-function genetic perturbations with separable spatial and temporal control. Importantly, our novel tool-set is independent of the commonly used GAL4/UAS system, freeing the latter for additional, non-autonomous, genetic manipulations; and is built into a single strain, allowing one-generation interrogation of non-autonomous effects. Altogether, our design opens up efficient genome-wide screens on any deleterious phenotype, once plasmid or genome engineering is used to place the desired miRNA(s) or ORF(s) into our genotype. Specifically, we developed tools to study extrinsic effects on neural tumor growth but the strategy presented has endless applications within and beyond neurobiology, and in other model organisms.

Original languageEnglish
JournaleLife
Volume7
Early online date27 Nov 2018
DOIs
Publication statusE-pub ahead of print - 27 Nov 2018

Fingerprint

Dive into the research topics of 'Spatiotemporally controlled genetic perturbation for efficient large-scale studies of cell non-autonomous effects'. Together they form a unique fingerprint.

Cite this