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Linneweber, G. A.

Publications and source records attributed to Linneweber, G. A..

5 recordsLinked to original sources

Increased variability and reduced phenotypic robustness in clonal Drosophila mercatorum

Quantitative genetics predicts that reducing genetic variability should reduce phenotypic variability, a common principle that underlies the widespread use of inbred, isogenic, and clonal animals in biomedical research. Yet extreme homozygosity can also expose recessive deleterious alleles and detoriate developmental buffering, potentially destabilizing rather than canalizing phenotypic outcomes. We tested this conflict directly in Drosophila mercatorum, a facultatively parthenogenic fly species in which pronuclear duplication results in fully homozygous, clonal offspring already after a single generation. Contrary to the expectation that genetic uniformity should reduce phenotypic variability, clonal parthenogenic flies showed changes in trait means, trait-dependent changes in interindividual variation, increased fluctuating asymmetry, and, most consistently, reduced behavioral and developmental canalization across a broad set of parameters. These effects on phenotypes spanned visually guided locomotion, circadian activity, wing morphology, bristle patterning, eye anatomy, brain volume, and serotonergic neuron numbers and were associated with reduced survival under environmental stress. Inbreeding of sexual D. mercatorum reproduced several of these phenotypic changes, whereas a single generation of outcrossing restored phenotypic robustness and the resulting F1 hybrids even exceeded the wild-type controls in several traits, consistent with a hybrid vigor effect. Together, these experiments identify loss of heterozygosity, rather than clonality per se, as the primary driver of developmental instability. Our findings show that genetic uniformity achieved through homozygosity can amplify stochastic phenotypic divergence by weakening developmental canalization, and suggest that the genetic context in which experimental standardization is achieved, especially heterozygosity, matters as much as the degree of genetic uniformity itself.

genetics↗

A minimal visual world model predicts exploration of naturalistic landscapes in flies

Animals, including small insects, can explore complex natural environments to locate resources and potential mates. How a miniaturized nervous system extracts actionable structure from complex visual scenes to guide effective exploration remains incompletely understood. To bridge the gap between behavioristic experimental control and ethological realism, we combined a virtual-reality flight assay with naturalistic three-dimensional environments based on high-resolution satellite imagery of real-world landscapes. Flies that had never experienced natural environments exhibited individually stable, non-random exploration patterns and preferred flying over vegetated and elevated terrain while avoiding water-like features, indicative of a minimalistic world model for ecologically relevant terrain selection. Flight paths were characterized by saccadic turns, which we analyzed in relation to visual scene components, including brightness, color composition, optic flow, elevation, and contrast. Using multivariable regression modeling, we identified a hierarchy of visual cues influencing saccade frequency, amplitude, and directionality, and mapped the retinal areas most strongly gating saccadic decision-making. We discovered individual differences in motion-sensitivity thresholds that predict stable individual exploration-exploitation phenotypes. indicating a population-level bet-hedging strategy to increase terrain coverage and resource encounter rates. Individuality-based probabilistic decision-making simulations, utilizing our hierarchical visual models, successfully replicated exploration behavior, with the predicted dispersal and trajectory statistics matching the empirical data and demonstrating generality even for visual assays not included in the training dataset. Our work links individual visual decision rules to efficient exploration mechanisms of large-scale natural landscapes, potentially inspiring neural circuit theory, ecological prediction frameworks, vision-based pest control, and energy-efficient autonomous system design.

neuroscience↗

Individuality across environmental context in Drosophila melanogaster

Over the past decade, several studies have demonstrated that idiosyncratic animal behaviors remain consistent over long time periods. The consistency of individually variable behaviors over time is often referred to as an animals individuality, or if consisting of multiple traits personality. However, most experimental 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 person-situation debate in humans and decades of observations of animal individuality under intrinsically variable natural conditions raise the question of whether and to what extent animal behavior remains consistent 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 demonstrate the relationship between individual behavior and variable environmental context under tightly controlled laboratory conditions in the model system Drosophila melanogaster. The consistency of three individual traits (termed exploration, attention, and anxiety) was investigated under changing environmental contexts (temperature, visual cues, arena shape), in both walking and flying flies. We find that individuality is highly context-dependent, but even under the most extreme environmental alterations tested, consistency of behavioral individuality always persisted in at least one of the traits. Furthermore, our quantification reveals a hierarchical order of environmental features influencing individuality. We confirmed this hierarchy using a generalized linear model and a hierarchical linear mixed model. In summary, our work demonstrates that, similar to humans, fly individuality persists across different contexts (albeit worse than across time), and individual differences shape behavior across variable environments. The presence of consistency across situations in flies makes the underlying developmental and functional mechanisms amenable to genetic dissection.

animal behavior and cognition↗

Variable brain wiring through scalable and relative synapse formation in Drosophila

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 DIP{gamma} mutant that ablates R7s preferred synaptic partner. Behaviorally, movement activity scales inversely with synapse numbers, while movement precision and relative connectivity are congruently robust. Hence, the fly genome encodes scalable relative connectivity to develop functional, but not identical, brains. One-Sentence SummaryNon-identical connectivity and behavior result from temperature-dependent synaptic partner availability in Drosophila.

neuroscience↗

Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring

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.

neuroscience↗