The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D

Cell Metabolism, Journal Year: 2017, Volume and Issue: 26(5), P. 719 - 737.e6

Published: Sept. 29, 2017

Elevated reactive oxygen species (ROS) induce the formation of lipids in neurons that are transferred to glia, where they form lipid droplets (LDs). We show glial and neuronal monocarboxylate transporters (MCTs), fatty acid transport proteins (FATPs), apolipoproteins critical for LD formation. MCTs enable glia secrete absorb lactate, which is converted pyruvate acetyl-CoA neurons. Lactate metabolites provide a substrate synthesis acids, processed by FATP apolipoproteins. In presence high ROS, inhibiting lactate transfer or lowering apolipoprotein levels decreases accumulation flies primary mouse glial-neuronal cultures. human APOE can substitute fly APOE4, an Alzheimer's disease susceptibility allele, impaired promotes neurodegeneration, providing insights into mechanisms.

Language: Английский

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A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila

eLife, Journal Year: 2015, Volume and Issue: 4

Published: March 31, 2015

Here, we document a collection of ∼7434 MiMIC (Minos Mediated Integration Cassette) insertions which 2854 are inserted in coding introns. They allowed us to create library 400 GFP-tagged genes. We show that 72% internally tagged proteins functional, and more than 90% can be imaged unfixed tissues. Moreover, the mRNAs knocked down by RNAi against GFP (iGFPi), efficiently deGradFP technology. The phenotypes associated with RNA protein knockdown typically correspond severe loss function or null mutant phenotypes. Finally, demonstrate reversible, spatial, temporal larvae adult flies. This new strategy strains allows unprecedented vivo manipulations flies for many These strategies will likely extend vertebrates.

Language: Английский

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Recent advances in neuropeptide signaling in Drosophila, from genes to physiology and behavior

Progress in Neurobiology, Journal Year: 2019, Volume and Issue: 179, P. 101607 - 101607

Published: March 22, 2019

Language: Английский

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A gene-specific T2A-GAL4 library for Drosophila

eLife, Journal Year: 2018, Volume and Issue: 7

Published: March 22, 2018

We generated a library of ~1000 Drosophila stocks in which we inserted construct the intron genes allowing expression GAL4 under control endogenous promoters while arresting transcription with polyadenylation signal 3' GAL4. This allows numerous applications. First, ~90% insertions essential cause severe loss-of-function phenotype, an effective way to mutagenize genes. Interestingly, 12/14 chromosomes engineered through CRISPR do not carry second-site lethal mutations. Second, 26/36 (70%) tested are rescued single UAS-cDNA construct. Third, phenotypes associated many can be reverted by excision UAS-flippase. Fourth, driven UAS-GFP/RFP reports tissue and cell-type specificity gene high sensitivity. report hundreds previously reported. Finally, cassettes replaced GFP or any DNA. These comprise powerful resource for assessing function.

Language: Английский

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Circadian neuron feedback controls the Drosophila sleep–activity profile

Nature, Journal Year: 2016, Volume and Issue: 536(7616), P. 292 - 297

Published: Aug. 1, 2016

Language: Английский

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Classifying Drosophila Olfactory Projection Neuron Subtypes by Single-Cell RNA Sequencing

Cell, Journal Year: 2017, Volume and Issue: 171(5), P. 1206 - 1220.e22

Published: Nov. 1, 2017

Language: Английский

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A genetic, genomic, and computational resource for exploring neural circuit function

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Jan. 15, 2020

The anatomy of many neural circuits is being characterized with increasing resolution, but their molecular properties remain mostly unknown. Here, we characterize gene expression patterns in distinct cell types the Drosophila visual system using genetic lines to access individual types, TAPIN-seq method measure transcriptomes, and a probabilistic interpret these measurements. We used tools build resource high-resolution transcriptomes for 100 driver covering 67 available at http://www.opticlobe.com. Combining recently reported connectomes helps how information transmitted processed across range scales, from synapses circuit pathways. describe examples that include identifying neurotransmitters, including cases apparent co-release, generating functional hypotheses based on receptor expression, as well strong commonalities between different types.

Language: Английский

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Genetic Reagents for Making Split-GAL4 Lines in Drosophila

Genetics, Journal Year: 2018, Volume and Issue: 209(1), P. 31 - 35

Published: March 13, 2018

Abstract The ability to reproducibly target expression of transgenes small, defined subsets cells is a key experimental tool for understanding many biological processes. Drosophila nervous system contains thousands distinct cell types and it has generally not been possible limit one or few when using single segment genomic DNA as an enhancer drive expression. Intersectional methods, in which the transgene only occurs where two different enhancers overlap their patterns, can be used achieve desired specificity. This report describes set over 2800 transgenic lines use with split-GAL4 intersectional method.

Language: Английский

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Advances in Engineering the Fly Genome with the CRISPR-Cas System

Genetics, Journal Year: 2018, Volume and Issue: 208(1), P. 1 - 18

Published: Jan. 1, 2018

Abstract Drosophila has long been a premier model for the development and application of cutting-edge genetic approaches. The CRISPR-Cas system now adds ability to manipulate genome with ease precision, providing rich toolbox interrogate relationships between genotype phenotype, delineate visualize how is organized, illuminate RNA, pioneer new gene drive technologies. Myriad transformative approaches have already originated from system, which will likely continue spark creation tools diverse applications. Here, we provide an overview editing revolutionized analysis in highlight key areas future advances.

Language: Английский

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An efficient CRISPR-based strategy to insert small and large fragments of DNA using short homology arms

eLife, Journal Year: 2019, Volume and Issue: 8

Published: Nov. 1, 2019

We previously reported a CRISPR-mediated knock-in strategy into introns of

Language: Английский

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