Gerit Linneweber | KU Leuven (original) (raw)

Papers by Gerit Linneweber

Research Square (Research Square), Feb 15, 2024

Over the past decade, several studies have demonstrated that idiosyncratic animal behaviors remai... more Over the past decade, several studies have demonstrated that idiosyncratic animal behaviors remain stable over long time periods. The stability of individually variable behaviors over time is often referred to as an animal's individuality, or personality. However, most studies have focused on individuality in a single, well-defined environmental context, whereas it is well-established from population studies that animal behavior is highly context-dependent. The ongoing 'person-situation debate' in humans raises the question whether also animal behavior remains stable across different situations, such as changing environmental contexts. For instance, one individual might be generally more visually guided than another, or rely only on one particular visual cue, or even on this very cue only in a specific environmental context. Here we use a combination of both well-established and novel behavioral assays to investigate the relationship between individual behavior and environmental context. The stability of three individual traits (exploration, attention, and anxiety) was investigated under changing environmental contexts (temperature, visual cues, arena shape), in both walking and flying Drosophila melanogaster. We find that individuality is highly context-dependent, but even under the most extreme environmental alterations tested, stability of behavior always persisted in at least one of the traits. Furthermore, our quantification reveals a hierarchical order of environmental features influencing individuality. In summary, our work demonstrates that similar to humans, animal individuality persists across different contexts, and individual differences shape behavior across variable environments.

bioRxiv (Cold Spring Harbor Laboratory), Apr 8, 2022

ABSTRACTThe emergence of neuronal wiring specificity requires stabilization of dynamic axonal bra... more ABSTRACTThe emergence of neuronal wiring specificity requires stabilization of dynamic axonal branches at sites of selective synapse formation. Models that explain how axonal branching is coupled to synaptogenesis postulate molecular regulators acting in a spatiotemporally restricted fashion. We report that Epidermal Growth Factor Receptor (EGFR) activity is required in presynaptic axonal branches during two distinct temporal intervals to regulate circuit wiring in the developing Drosophila visual system. EGFR is required early to regulate primary axonal branching and independently again later to prevent autophagic degradation of the synaptic active zone protein Bruchpilot (Brp). The protection of synaptic material during this later interval of wiring ensures the stabilization of terminal branches, circuit connectivity and appropriate visual behavior. Phenotypes of EGFR inactivation were rescued by increasing Brp levels or downregulating autophagic genes. We identify a temporally restricted molecular mechanism required for coupling axonal branching and synaptic stabilization that contributes to the emergence of neuronal wiring specificity.

bioRxiv (Cold Spring Harbor Laboratory), Feb 5, 2019

The genome versus experience, or "Nature versus Nurture", debate has dominated our understanding ... more The genome versus experience, or "Nature versus Nurture", debate has dominated our understanding of individual behavioral variation. A third factor, namely variation in complex behavior potentially due to non-heritable "developmental noise" in brain development, has been largely ignored. Using the Drosophila vinegar fly we demonstrate a causal link between variation in brain wiring due to developmental noise, and behavioral individuality. A population of visual system neurons called DCNs shows non-heritable, inter-individual variation in right/left wiring asymmetry, and control object orientation in freely walking flies. We show that DCN wiring asymmetry predicts an individual's object responses: the greater the asymmetry, the better the individual orients. Silencing DCNs abolishes correlations between anatomy and behavior, while inducing visual asymmetry via monocular deprivation "rescues" object orientation in DCN-symmetric individuals.

PLOS ONE, Jun 8, 2015

Most animal tissues and organ systems are comprised of highly ordered arrays of varying cell type... more Most animal tissues and organ systems are comprised of highly ordered arrays of varying cell types. The development of external sensory organs requires complex cell-cell communication in order to give each cell a specific identity and to ensure a regular distributed pattern of the sensory bristles. This involves both long and short range signaling mediated by either diffusible or cell anchored factors. In a variety of processes the heterophilic Irre Cell Recognition Module, consisting of the Neph-like proteins: Roughest, Kin of irre and of the Nephrin-like proteins: Sticks and Stones, Hibris, plays key roles in the recognition events of different cell types throughout development. In the present study these proteins are apically expressed in the adhesive belt of epithelial cells participating in sense organ development in a partially exclusive and asymmetric manner. Using mutant analysis the GAL4/UAS system, RNAi and gain of function we found an involvement of all four Irre Cell Recognition Module-proteins in the development of a highly structured array of sensory organs in the wing disc. The proteins secure the regular spacing of sensory organs showing partial redundancy and may function in early lateral inhibition events as well as in cell sorting processes. Comparisons with other systems suggest that the Irre Cell Recognition module is a key organizer of highly repetitive structures.

Science, Mar 6, 2020

bioRxiv (Cold Spring Harbor Laboratory), Sep 8, 2019

Brain wiring is remarkably precise, yet most neurons readily form synapses with incorrect partner... more Brain wiring is remarkably precise, yet most neurons readily form synapses with incorrect partners when given the opportunity. Dynamic axon-dendritic positioning can restrict synaptogenic encounters, but the spatiotemporal interaction kinetics and their regulation remain essentially unknown inside developing brains. Here we show that the kinetics of axonal filopodia restrict synapse formation and partner choice for neurons that are not otherwise prevented from making incorrect synapses. Using 4D imaging in developing Drosophila brains, we show that filopodial kinetics are regulated by autophagy, a prevalent degradation mechanism whose role in brain development remains poorly understood. With surprising specificity, autophagosomes form in synaptogenic filopodia, followed by filopodial collapse. Altered autophagic degradation of synaptic building material quantitatively regulates synapse formation as shown by computational modeling and genetic experiments. Increased filopodial stability enables incorrect synaptic partnerships. Hence, filopodial autophagy restricts inappropriate partner choice through a process of kinetic exclusion that critically contributes to wiring specificity.

(A) The Drosophila IRM-proteins consist of the Neph-like proteins Rst... more (A) The Drosophila IRM-proteins consist of the Neph-like proteins Rst and Kirre and of the Nephrin-like proteins Hbs and SNS. (B) Representative image showing the three bristle rows of the anterior wing margin [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128490#pone.0128490.ref005" target="_blank">5</a>]. The dorsal row consists of recurved bristles marked with an arrow. The medial row consists of mechanosensory stout bristles. The ventral row is composed of mechanosensory slender bristles and recurved bristles marked with an arrow. (C) Representative image of the presumptive wing margin of a late third instar larvae. Kirre in blue can be found in the presumptive posterior wing margin (pwm), anterior wing margin (awm) and the wing veins L3, L4 and L5. SNS in yellow can be only found in the SOPs of the awm. Six example SOPs are marked with an arrow. The ventral (v) side faces up and dorsal (d) faces down. (D-E) The apical localization of the IRM-protein Rst (red) is shown in third instar larvae of the genotype neur-GAL4>UAS-mCD8-GFP (green). The SOPs are specifically marked by GFP. The images show a 3D reconstruction in (D) and a lateral view (E). (F-I) Localization of the IRM-proteins in the awm of third instar larvae. Rst (F) in red is localized in two adhesive belts in the awm and is enriched at the border to the SOPs of the recurved bristles. neur-GAL4>UAS-rst-RNAi shows no effect on the enrichment of staining around the SOPs (F’). A similar staining pattern in green can be seen for Hbs in wild type (G), but the SOP specific RNAi shows a reduction of staining around the SOP borders (G’), indicating Hbs expression inside the SOPs. Kirre in blue (H) shows a similar pattern as Rst and SOP specific RNAi has no effect (H’). SNS (I) in yellow can only be found at the border of the SOPs. neur-GAL4>UAS-sns-RNAi reduces SNS in the SOPs (I’). Scale bars correspond to 10μm in all images.</p

SSRN Electronic Journal

The emergence of neuronal wiring specificity requires stabilization of dynamic axonal branches at... more The emergence of neuronal wiring specificity requires stabilization of dynamic axonal branches at sites of selective synapse formation. Models that explain how axonal branching is coupled to synaptogenesis postulate molecular regulators acting in a spatiotemporally restricted fashion. We report that Epidermal Growth Factor Receptor (EGFR) activity is required in presynaptic axonal branches during two distinct temporal intervals to regulate circuit wiring in the developing Drosophila visual system. EGFR is required early to regulate primary axonal branching and independently again later to prevent autophagic degradation of the synaptic active zone protein Bruchpilot (Brp). The protection of synaptic material during this later interval of wiring ensures the stabilization of terminal branches, circuit connectivity and appropriate visual behavior. Phenotypes of EGFR inactivation were rescued by increasing Brp levels or downregulating autophagic genes. We identify a temporally restricted molecular mechanism required for coupling axonal branching and synaptic stabilization that contributes to the emergence of neuronal wiring specificity.

PLoS computational biology, Jan 30, 2018

Isolation profoundly influences social behavior in all animals. In humans, isolation has serious ... more Isolation profoundly influences social behavior in all animals. In humans, isolation has serious effects on health and disease. 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 a...

Current biology : CB, Jan 23, 2017

Fragile X syndrome (FXS) patients present neuronal alterations that lead to severe intellectual d... more 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 autis...

PloS one, 2015

The genome versus experience, or “Nature versus Nurture”, debate has dominated our understanding ... more The genome versus experience, or “Nature versus Nurture”, debate has dominated our understanding of individual behavioral variation. A third factor, namely variation in complex behavior potentially due to non-heritable “developmental noise” in brain development, has been largely ignored. Using the Drosophila vinegar fly we demonstrate a causal link between variation in brain wiring due to developmental noise, and behavioral individuality. A population of visual system neurons called DCNs shows non-heritable, inter-individual variation in right/left wiring asymmetry, and control object orientation in freely walking flies. We show that DCN wiring asymmetry predicts an individual’s object responses: the greater the asymmetry, the better the individual orients. Silencing DCNs abolishes correlations between anatomy and behavior, while inducing visual asymmetry via monocular deprivation “rescues” object orientation in DCN-symmetric individuals.One Sentence SummaryNon-heritable individual ...

eLife

Rab GTPases are molecular switches that regulate membrane trafficking in all cells. Neurons have ... more 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 rab genes in Drosophila. In flies, all rab 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 rab26. The complete mutant collection generated in this study provides a basis for further c...

bioRxiv, 2021

Variability of synapse numbers and partners despite identical genes reveals limits of genetic det... more Variability of synapse numbers and partners despite identical genes reveals limits of genetic determinism. Non-genetic perturbation of brain wiring can therefore reveal to what extent synapse formation is precise and absolute, or promiscuous and relative. Here, we show the role of relative partner availability for synapse formation in the fly brain through perturbation of developmental temperature. Unexpectedly, slower development at lower temperatures substantially increases axo-dendritic branching, synapse numbers and non-canonical synaptic partnerships of various neurons, while maintaining robust ratios of canonical synapses. Using R7 photoreceptors as a model, we further show that scalability of synapse numbers and ratios is preserved when relative availability of synaptic partners is changed in a DIPγ mutant that ablates R7’s preferred synaptic partner. Behaviorally, movement activity scales inversely with synapse numbers, while movement precision and relative connectivity are ...

Nature Communications