Proper organ shape is critical for function. The Drosophila wing normally adopts an elongated shape, but mutations in the Dachsous-Fat pathway result in rounder wings. The mechanism by which this occurs has remained unclear. Here, we show that Ds-Fat signaling shapes the wing during the larval stage, rather than during pupal development when morphogenetic rearrangements transform the developing wing disc into the adult wing. We further find that Ds-Fat alters tissue-wide stresses in the wing disc, and genetic manipulations that reduce cytoskeletal tension result in rounder wings, whereas increasing cytoskeletal tension produces more elongated wings. Reduced tension is also associated with less oriented growth during development. Notably, increased cytoskeletal tension partially rescues the rounder shape caused by ds knockdown. These results reveal a previously unrecognized mechanism by which Ds-Fat signaling determines wing shape, involving regulation of tissue tension to orient growth and shape the wing primordia during larval development.

As a hallmark of avian ecological innovation, powered flight has fundamentally shaped diverse aspects of birds. The energy demand of flight may have mutagenic impacts on genomes, influencing how fast genomes evolve. However, the relationship between flight, metabolism, and evolutionary rates remains relatively underexplored. Leveraging 363 newly available avian genomes from >90% of avian families, we quantified three distinct types of genomic evolutionary rates to capture a broad spectrum of mutational processes. By combining four flight-related traits and three metabolic metrics, we uncovered significant associations between flight style, metabolism, and multiple evolutionary rates. Next, using a causal inference framework, we demonstrated that metabolism accounted for 43.3% of the total effect between flight and evolutionary rate, underscoring its key role. Together, our findings establish a robust connection between flight, metabolism, and evolutionary rates, offering new insights into how key innovations and associated phenotypes shape the tempo of genome evolution.

Social interactions are essential for survival in primates, relying on both facial expressions and body signals. The accurate characterization of these signals is critical for understanding the neurocomputational mechanisms underlying social communication. While previous work has focused on recognizing monkey behavior, a causal and direct manipulation of individual cues strongly benefits from believable, dynamic body avatars-analogous to those successfully developed for faces. Creating lifelike monkey avatars with realistic body motion, however, is challenging. Acquiring sufficiently accurate movement data for animation with marker-based motion capture is impractical, and markerless tracking methods require extensive manual labeling. To address this, we developed MacAction, a realistic macaque body avatar animated from multi-camera markerless tracking data. Our method reconstructs accurate trajectories for a large number of keypoints, as required for the 3D animation of realistic body models. The entire time course of individual actions is captured using only two labeled keyframes per second, with performance further validated on a large-scale human multi-view dataset. We assessed the animation quality of our dynamic avatar in a free-viewing experiment with eight macaque observers for single macaque actions, where fixation behavior was indistinguishable between our animations and matched real videos. Moreover, by systematically varying the realism of the avatar, we found an uncanny valley effect in macaque body perception, similar to that previously described in both humans and macaque faces. These findings support the commonalities of social vision across primate species, providing a foundation for controlled experiments aimed at clarifying the detailed neurocomputational mechanisms of social body perception in primates.

Olfactory childhood memories are particularly important for forming one's identity. However, we don't know how they exert their privileged influence and shape brain structure. To address this, we modeled childhood olfactory memory in mice based on a human survey indicating that our earliest olfactory memory arises from repeated positive experiences paired with a pleasant odorant. Accordingly, mice were exposed during childhood to an attractive odorant in a playful environment. In adulthood, memory recall relied on neonatal-born granule cells (GCs) in the olfactory bulb, as their optogenetic silencing impaired retrieval, and on increased functional connectivity in the reward system. With age, memory persistence depended on re-exposure to the childhood odorant and was associated with the disengagement of neonatal-born GCs, alongside with strengthened limbic functional connectivity. Together, these findings identify neonatal neurons as a key substrate for encoding childhood olfactory memory and reveal dynamic reorganization of brain networks supporting its long-term significance.

The development of the complex nervous system is strictly controlled by diverse isoforms produced from individual genes, but the underlying machinery remains unclear. Our long-read cDNA sequencing of mouse cerebellar granule cell progenitors (GCPs) identifies more than 700 genes with high isoform diversity. One such gene, Meis1, produces MEIS1-FL and MEIS1-HdL isoforms, which include and lack the homeodomain, respectively. Our previous study showed that MEIS1-FL localizes to nuclei and promotes ATOH1 protein degradation through transcriptional regulation, thereby promoting GCP differentiation. In contrast, our in vivo electroporation experiments in the postnatal mouse cerebellum show that MEIS1-HdL inhibits GCP differentiation. MEIS1-HdL localizes in the cytoplasm and inhibits the degradation of ATOH1 mediated by CUL3, which is a newly identified E3 ligase for ATOH1. MEIS1-HdL enhances the binding of the COP9 signalosome to CUL3, which suppresses ATOH1 polyubiquitination. This study demonstrates that functionally antagonistic isoforms derived from a single gene cleverly control neural progenitor differentiation.

Observing immoral behavior increases one's dishonesty by social influence and learning processes. The neurocomputational mechanisms underlying such moral contagion remain unclear. We tested different mechanistic hypotheses to account for moral contagion. We used model-based fMRI and a new cheating game in which participants were sequentially placed in honest and dishonest social norm contexts. Participants' cheating behavior increased in the dishonest norm context but was unchanged in the honest one. The best model to account for behavior indicated that participants' valuation was dynamically biased by learning that others had cheated. At the group level, this valuation bias was not encoded by any specific brain region. Instead, this neural signal depended on individual differences in conformity, and engaged the bilateral lateral prefrontal cortex. During learning, simulation of others' cheating behavior was encoded in the posterior superior temporal sulcus. Together, these findings provide a mechanistic understanding of how learning about others' dishonesty biases individuals' valuation of cheating but does not alter one's established preferences.

Neuroeconomics has long focused on reward values, ignoring their identity. A new PLOS Biology study shows that identity-specific reward expectations in the lateral orbitofrontal cortex steer goal-directed choices through a motivational circuit involving the nucleus accumbens.

Flight has been a key innovation in insect evolution, yet the selective and mechanistic pressures shaping their flight motor systems remain poorly understood. Here, we present a comprehensive comparative analysis of flight in Diptera (true flies), integrating morphology, wingbeat kinematics, and aerodynamics within a phylogenetic framework. We quantified morphology in 133 species spanning the Dipteran phylogenetic and size range, and for a subset of 46 species, we combined high-speed stereoscopic videography with computational fluid dynamics (CFD) to characterize wingbeat kinematics and aerodynamic performance, respectively. Our results reveal that morphology is strongly structured by phylogeny, whereas wingbeat kinematics are broadly conserved across Diptera, reflecting dominant aerodynamic constraints. Two early-diverged lineages, Culicomorpha (mosquitoes and midges) and Tipulomorpha (crane flies), exhibit strikingly divergent kinematics and aerodynamics, suggesting lineage-specific selective pressures. Combining these data with scaling analyses shows that maintaining in-flight weight support across the dipteran size range requires systematic allometric adjustments in wing morphology, wingbeat kinematics, and flight musculature. Smaller dipterans achieve weight support through relatively larger wings and higher wingbeat frequencies, whereas larger dipterans achieve the same aerodynamic requirement through increased investment in flight musculature to sustain the necessary mechanical power output. These size-dependent trait combinations highlight how different morphological and kinematic adaptations evolved in response to the shared physical requirements of hovering flight across Diptera. Mosquitoes and midges represent an extreme case, exhibiting a pronounced aerodynamic-acoustic trade-off with disproportionately high wingbeat frequencies, large flight musculature and increased aerodynamic and acoustic power, consistent with selection favoring acoustic signaling during in-swarm mating. By integrating comparative morphology, kinematics, and aerodynamics across a major insect radiation, our study uncovers the interplay between physical scaling laws, aerodynamic constraints, and ecological pressures in shaping the evolution of animal flight. These findings provide a mechanistic framework for understanding how complex locomotor systems diversify under multiple selection pressures.

Real-life decisions are typically directed toward specific types of rewards (e.g., a slice of pizza or a bowl of pasta), but reward identity is often neglected in neuroeconomic theories of decision-making. Previous research has shown that the lateral orbitofrontal cortex (lOFC) represents the specific rewards predicted by environmental cues. However, whether and how these expectations influence decision-making remains an open question. To address these questions in humans, we developed a novel behavioral task in which Pavlovian cues associated with specific rewards are presented before participants can make decisions to forage these rewards. Using pattern-based analysis of functional magnetic resonance imaging data, we show that cues predicting distinct reward types evoke identity-specific expectations in lOFC, which in turn predict subsequent choices. This effect is amplified by activity in the nucleus accumbens, which enhances the influence of lOFC reward expectations on action representations in the dorsal anterior cingulate cortex. These results connect representational and motivational accounts of decision-making, highlighting the neural mechanism by which expectations about reward identity guide goal-directed behavior.

The sleep-wake cycle is generated by competing neural circuits that control the oscillation between wakefulness, rapid eye movement (REM) sleep, and non-REM (NREM) sleep. While the sublaterodorsal tegmental nucleus (SLD) is recognized for its role in REM sleep generation, the functional contribution of its GABAergic neurons (SLDGABA) to sleep-wake regulation remains poorly understood. Here, we found that SLDGABA neurons function as a suppressor of wakefulness in both healthy (i.e., orexin+/+) and narcoleptic (i.e., orexin-/-) mice. In healthy mice, optogenetic silencing of SLDGABA neurons rapidly induced robust wakefulness, while enhancing cortical and motor activity. Conversely, optogenetic activation of these neurons suppressed wakefulness and promoted NREM sleep. We found traces of SLDGABA axonal projections to wake-promoting brain regions, providing an anatomical basis for their wake-suppressing effects. Importantly, we discovered that SLDGABA neurons play a pathological role in narcolepsy: their activation in orexin-deficient narcoleptic mice triggered characteristic sleep attacks-rapid intrusions of NREM sleep during active wakefulness-while silencing these neurons rescued animals from both sleep attacks and cataplexy. Collectively, these findings establish SLDGABA neurons as a key regulator of arousal state transitions and identify them as a novel therapeutic target for the treatment of narcolepsy.

The circadian system synchronizes physiology, improving the adaptation to daily environmental changes. In mammals, the central pacemaker, in the suprachiasmatic nuclei (SCN) of the hypothalamus, coordinates "wake" functions by inducing the circadian release of glucocorticoids (GCs). GCs entrain the clocks of a wide variety of tissues through GC receptor (GR) activation, however, the influence of GCs on the SCN is unclear and seems to depend on the maturity of the circuit. During the perinatal period, the mouse SCN express GR and respond directly to GCs while the adult SCN express low GR and have been traditionally considered resistant to GCs. To understand the change of sensitivity to GCs we followed the developmental trajectory of the mouse SCN, and found that while GR is expressed in all SCN cells early in life, it remains expressed mainly in astrocytes in the adult. Using a model of prenatal exposure to GCs, we found that offspring from treated mothers, adapt slower to shifted light-dark cycle and shows reduced expression of GR in SCN astrocytes. The adult SCN astrocytes can indeed sense and respond to GCs with rapid astrocytic Ca2+ events that propagate across neighboring cells, an effect that is prevented by the specific inhibition of astrocyte-astrocyte communication. Our findings provide a conceptual advance on how the mouse clock develops and on the influence that GCs have on the SCN. This might be relevant to understand how circadian synchrony is restored in conditions of temporal misalignment, such as jet lag.

In some forms of postdictive phenomena, later events influence the perception of earlier ones, suggesting that conscious perception may be preceded by extended periods of unconscious processing. An example is the Sequential Metacontrast (SQM) paradigm, in which vernier offsets are unconsciously integrated over several hundred milliseconds before conscious perception. Obviously, the integrated percept can only emerge after each individual element in the stream has been processed. Thus, the SQM provides a unique opportunity to dissociate unconscious from conscious stages of visual processing, as these stages are well separated in time. Using electroencephalography (EEG) recordings in human participants during the SQM, we identified two distinct stages of neural activity: an early occipital EEG activity pattern (~200 ms after the initial vernier) associated with unconscious processing, and a later centro-parietal EEG pattern (~400 to 600 ms after SQM onset) associated with the integrated percept and the behavioral report. We propose that the transition between these neural patterns marks the shift from unconscious encoding of individual visual stimuli to their integrated percept.

CRISPR-based gene drives are selfish genetic elements with the potential to spread through entire insect populations for sustainable vector control. Gene drives designed to disrupt the reproductive capacity of females can suppress laboratory populations of the malaria mosquito, Anopheles gambiae. However, any suppressive intervention will inevitably exert an evolutionary pressure for resistance, and the likelihood of resistance emerging at natural population scales remains poorly defined. Here, we present a pipeline to quantify the evolutionary space for resistance, enabling accelerated discovery, engineering, and testing of both natural and drive-induced variants that could reverse gene drive spread. We applied our approach to stress-test a best-in-class suppression gene drive that has evaded resistance in all laboratory-contained releases to date, known as Ag(QFS)1. We showed that previously undetected resistant alleles can arise at low frequency, including a novel type of partially resistant alleles that can perturb drive-invasion dynamics. Integrating experimentally derived resistance rates with population genetic modeling shows that single-target suppression drives are unlikely to be robust at natural mosquito population sizes, even at highly constrained loci. Here, we engineer and validate multiplexed gene drives in Anopheles gambiae, that target multiple conserved sites, actively removing resistant alleles. Our models predict that such gene drives could supress large natural mosquito populations in the field.

Shared memories of event details are crucial to eyewitness testimony. When different people encode or recall the same event, similar scene-specific neural activity patterns emerge across individual brains. However, it remains unclear whether these patterns are specific to event details and how test expectancy (i.e., expecting free recall or general memory tests) and misinformation affect them. In this study, 100 participants were randomly assigned to view one of two versions of each event. Both versions featured identical scenarios, but with different details. About half of the participants were informed about the upcoming free recall before viewing events, while the others were told to expect a general memory test. Functional magnetic resonance imaging was used to record their brain activity during four stages: viewing original events, initial free recall, reading misinformation, and final free recall of original events. The neuroimaging data were analyzed based on the similarity of neural patterns across participants. Test expectancy increased the similarity of detail-specific neural activity patterns between individuals when they viewed original events in brain regions relevant for visual attention. Misinformation increased the likelihood of people forming shared false memories of event details. People who formed shared false memories exhibited similar detail-specific patterns of activity in the dorsomedial prefrontal cortex when reading misinformation. People who formed shared true memories exhibited similar detail-specific patterns of activity in the inferior parietal lobe when viewing original events, as well as in the ventrolateral prefrontal cortex and middle temporal gyrus when recalling them after exposure to misinformation. Our findings revealed that different brain regions of the default mode network play distinct roles in the encoding and recall of event details shared by individuals.

Why do even closely-related bacteria differ in their capacity to evolve antibiotic resistance? Drawing on evidence from experimental evolution, pathogen genomics, and molecular microbiology, this Essay argues that the evolution of antibiotic resistance in bacterial genomes is frequently catalyzed by the presence of 'resistance potentiators': genes, elements, or pathways that accelerate evolution in a trait-specific manner. Epidemiological evidence suggests that resistance potentiators that modulate phenotypes have been particularly important in successful pathogen lineages. Furthermore, experimental models show that combining antibiotics with inhibitors of resistance potentiators can restrict the evolution of resistance, suggesting that they could be future drug targets or otherwise lead to more evolution-informed antibiotic therapy.