Publications by authors named "Gerit A Linneweber"

5 Publications

  • Page 1 of 1

Systematic functional analysis of rab GTPases reveals limits of neuronal robustness to environmental challenges in flies.

Elife 2021 03 5;10. Epub 2021 Mar 5.

Division of Neurobiology, Institute for Biology, Freie Universität Berlin, Berlin, Germany.

Rab GTPases are molecular switches that regulate membrane trafficking in all cells. Neurons have particular demands on membrane trafficking and express numerous Rab GTPases of unknown function. Here, we report the generation and characterization of molecularly defined null mutants for all 26 genes in . In flies, all genes are expressed in the nervous system where at least half exhibit particularly high levels compared to other tissues. Surprisingly, loss of any of these 13 nervous system-enriched Rabs yielded viable and fertile flies without obvious morphological defects. However, all 13 mutants differentially affected development when challenged with different temperatures, or neuronal function when challenged with continuous stimulation. We identified a synaptic maintenance defect following continuous stimulation for six mutants, including an autophagy-independent role of The complete mutant collection generated in this study provides a basis for further comprehensive studies of Rab GTPases during development and function in vivo.
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http://dx.doi.org/10.7554/eLife.59594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016483PMC
March 2021

A simple computer vision pipeline reveals the effects of isolation on social interaction dynamics in Drosophila.

PLoS Comput Biol 2018 08 30;14(8):e1006410. Epub 2018 Aug 30.

VIB Center for the Biology of Disease, VIB, Leuven, Belgium.

Isolation profoundly influences social behavior in all animals. In humans, isolation has serious effects on health. Drosophila melanogaster is a powerful model to study small-scale, temporally-transient social behavior. However, longer-term analysis of large groups of flies is hampered by the lack of effective and reliable tools. We built a new imaging arena and improved the existing tracking algorithm to reliably follow a large number of flies simultaneously. Next, based on the automatic classification of touch and graph-based social network analysis, we designed an algorithm to quantify changes in the social network in response to prior social isolation. We observed that isolation significantly and swiftly enhanced individual and local social network parameters depicting near-neighbor relationships. We explored the genome-wide molecular correlates of these behavioral changes and found that whereas behavior changed throughout the six days of isolation, gene expression alterations occurred largely on day one. These changes occurred mostly in metabolic genes, and we verified the metabolic changes by showing an increase of lipid content in isolated flies. In summary, we describe a highly reliable tracking and analysis pipeline for large groups of flies that we use to unravel the behavioral, molecular and physiological impact of isolation on social network dynamics in Drosophila.
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http://dx.doi.org/10.1371/journal.pcbi.1006410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135522PMC
August 2018

Reduced Lateral Inhibition Impairs Olfactory Computations and Behaviors in a Drosophila Model of Fragile X Syndrome.

Curr Biol 2017 Apr 30;27(8):1111-1123. Epub 2017 Mar 30.

Neuroelectronics Research Flanders (NERF), KU Leuven, Kapeldreef 75, 3001 Leuven, Belgium; Kavli Institute for Systems Neuroscience and Centre for Neural Computation, NTNU, Olav Kyrres gate 9, 7030 Trondheim, Norway. Electronic address:

Fragile X syndrome (FXS) patients present neuronal alterations that lead to severe intellectual disability, but the underlying neuronal circuit mechanisms are poorly understood. An emerging hypothesis postulates that reduced GABAergic inhibition of excitatory neurons is a key component in the pathophysiology of FXS. Here, we directly test this idea in a FXS Drosophila model. We show that FXS flies exhibit strongly impaired olfactory behaviors. In line with this, olfactory representations are less odor specific due to broader response tuning of excitatory projection neurons. We find that impaired inhibitory interactions underlie reduced specificity in olfactory computations. Finally, we show that defective lateral inhibition across projection neurons is caused by weaker inhibition from GABAergic interneurons. We provide direct evidence that deficient inhibition impairs sensory computations and behavior in an in vivo model of FXS. Together with evidence of impaired inhibition in autism and Rett syndrome, these findings suggest a potentially general mechanism for intellectual disability.
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http://dx.doi.org/10.1016/j.cub.2017.02.065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405172PMC
April 2017

Neuronal control of metabolism through nutrient-dependent modulation of tracheal branching.

Cell 2014 Jan;156(1-2):69-83

Gut Signalling and Metabolism Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK. Electronic address:

During adaptive angiogenesis, a key process in the etiology and treatment of cancer and obesity, the vasculature changes to meet the metabolic needs of its target tissues. Although the cues governing vascular remodeling are not fully understood, target-derived signals are generally believed to underlie this process. Here, we identify an alternative mechanism by characterizing the previously unrecognized nutrient-dependent plasticity of the Drosophila tracheal system: a network of oxygen-delivering tubules developmentally akin to mammalian blood vessels. We find that this plasticity, particularly prominent in the intestine, drives--rather than responds to--metabolic change. Mechanistically, it is regulated by distinct populations of nutrient- and oxygen-responsive neurons that, through delivery of both local and systemic insulin- and VIP-like neuropeptides, sculpt the growth of specific tracheal subsets. Thus, we describe a novel mechanism by which nutritional cues modulate neuronal activity to give rise to organ-specific, long-lasting changes in vascular architecture.
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http://dx.doi.org/10.1016/j.cell.2013.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898607PMC
January 2014

Remote control of renal physiology by the intestinal neuropeptide pigment-dispersing factor in Drosophila.

Proc Natl Acad Sci U S A 2012 Jul 9;109(30):12177-82. Epub 2012 Jul 9.

Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.

The role of the central neuropeptide pigment-dispersing factor (PDF) in circadian timekeeping in Drosophila is remarkably similar to that of vasoactive intestinal peptide (VIP) in mammals. Like VIP, PDF is expressed outside the circadian network by neurons innervating the gut, but the function and mode of action of this PDF have not been characterized. Here we investigate the visceral roles of PDF by adapting cellular and physiological methods to the study of visceral responses to PDF signaling in wild-type and mutant genetic backgrounds. We find that intestinal PDF acts at a distance on the renal system, where it regulates ureter contractions. We show that PdfR, PDF's established receptor, is expressed by the muscles of the excretory system, and present evidence that PdfR-induced cAMP increases underlie the myotropic effects of PDF. These findings extend the similarities between PDF and VIP beyond their shared central role as circadian regulators, and uncover an unexpected endocrine mode of myotropic action for an intestinal neuropeptide on the renal system.
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http://dx.doi.org/10.1073/pnas.1200247109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409758PMC
July 2012
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