Epithelial fusion is critical for formation of many embryonic tissues. The developing mammalian spinal cord fuses by zippering, through cell behaviours dependent on F-actin turnover. We propose a caudal-to-rostral sequence of surface ectoderm cell behaviours which drive zippering progression in mice, and test the requirement for the F-actin severing protein CFL1 in this process. Key zipper-advancing behaviours are: (i) constriction of supracellular actomyosin cables; (ii) extension of filopodial/lamellipodial protrusions at periodic intervals; (iii) constriction of leading-edge cell borders bringing together protrusions which establish 'pioneering' contacts across the midline; (iv) cell-cell and v. cell-ECM adhesion remodelling; (vi) zipper advancement through cell partner exchange. In wild-type embryos, CFL1 is enriched at the leading edge of surface ectoderm cells adjacent to the zippering point and localised within some protrusions. Conditional Cfl1 deletion in the surface ectoderm produces denser F-actin stress fibres, makes filopodial protrusions excessively stable, diminishes their exploratory movements which may establish nascent contacts, and impairs junctional constriction of cells at the point of fusion. Zippering speed is reduced ~30% in conditional Cfl1-deleted embryos and ~30% develop spina bifida. We therefore propose that impaired filopodial dynamicity and junctional constriction limits the sequence of behaviours driving spinal zippering, predisposing to spina bifida.

Only a fraction of bacterial genomes encode CRISPR-Cas systems, but the selective causes of this variation are unexplained. How naturally virulent bacteriophages (phages) select for CRISPR immunity has rarely been tested experimentally. Here, we show against a panel of genetically and functionally diverse virulent phages that CRISPR immunity was not universally beneficial to Pseudomonas aeruginosa, and its fitness effect varied strongly between phages in predictable ways. In addition to mechanisms known to alter the effectiveness of CRISPR immunity, such as encoding a matching spacer or a protective nuclear shell, we show that the fitness effect of CRISPR immunity negatively associated with the probability of evolving receptor-based resistance to the phage via spontaneous mutation. The supply of resistance mutations differed strongly between very closely related lipopolysaccharide-binding phages and was associated with variation at the C-terminus of the tail fibre protein altering residues involved in hydrogen bonding and the predicted binding site. Our results show that CRISPR immunity is more beneficial against virulent phages that are harder to evolve resistance to via receptor mutations, suggesting that virulent phage community composition and diversity will be important drivers of the prevalence of CRISPR immunity.

In animal development, cells exit the cell cycle after a final round of cell division to differentiate into specialized cell types. However, the impact of failed cytokinesis on the fate specification of postmitotic cells, especially neurons, remains poorly understood. We analyzed the Caenorhabditis elegans mutants lacking the midbody-tethered endonuclease LEM-3/ANKLE1, which resolves chromatin bridges during cytokinesis. Using genetic analysis, fluorescence microscopy, and RNA visualization, we found that unresolved DNA bridges lead to the formation of stable intercellular bridges, creating binucleate syncytia between touch receptor neurons and sister cells, which allows thorough cytoplasmic mixing despite independent nuclear transcription. In some cases, the cytoplasmic linkage between sister cells also led to the suppression of neuronal fates and prevention of apoptotic fates. Thus, LEM-3 prevents syncytium formation to ensure proper cellular differentiation.

Human emotional experiences vary widely in everyday life, yet they are systematically organized within a continuous affective space defined by valence and arousal. Although this circumplex organization has shaped decades of research, its neural implementation remains unclear. Here, we asked whether abstract emotion concepts are encoded using grid-like coordinate principles in the human brain. During fMRI, participants tracked trajectories through affective space conveyed through morphs of facial expressions and sequences of phrases. We found that ventromedial prefrontal cortex (vmPFC) encoded affective space with robust hexadirectional modulation characteristic of grid-like coding. This coordinate representation generalized across stimulus modalities, indicating abstraction beyond perceptual features. The grid-like signal reflected a metric organization of emotion concepts independent of overt behavior, whereas distance-related signals in vmPFC predicted trial-by-trial affective judgements. Together, these findings suggest that emotion knowledge is structured by a grid-like coordinate system in the human brain that can support predictive inference and flexible decision-making.

Gut symbionts condition mucosal immunity to resist infection by enteropathogens, but the specific microbes and mechanisms involved differ significantly between host species. In higher primates, bacterial metabolite HMB-PP is sensed by a specialized population of Vγ9Vδ2+T-cells, which we now report can potently suppress growth of endogenous fungi in human intestinal organ cultures. In healthy intestine, HMB-PP-stimulated Vδ2+ T-cells restricted outgrowth of keystone fungus Candida albicans via a mechanism that required IL-22. In Crohn's disease (CD), Vδ2+ T-cells were poorly responsive to HMB-PP and permitted outgrowth of C. albicans strains that formed toxin-producing filaments, triggered neutrophil extracellular traps, and induced macrophage IL-1β release ex vivo. Genomic and proteomic analysis of the Candida isolates suggested increased tissue adhesion of CD-derived strains, which rapidly invaded the gut barrier in an 'intestine-on-a-chip' model. These data reveal that bacterial activation of Vδ2+ T-cells suppresses fungal pathobionts in human gut via an IL-22-dependent mechanism that is dysregulated in CD.

Microbes are increasingly recognized as modulators of host behavior, but the underlying mechanisms are poorly understood. A new PLOS Biology study reveals a microbiome-to-gut-to-neuron pathway linking developmental microbial exposure to later food avoidance.

Research into neurodegeneration is often confined to a single disease, cell type or mechanism. A new collection of articles explores neurodegeneration within its physiological context, looking beyond diseased neurons to the surrounding tissue microenvironment.

A common explanation for bats being a conspicuous source of zoonotic viruses is their purported ability to coexist with viruses without suffering overt disease. Widespread acceptance of the idea that bats have unusual antiviral traits has catalyzed the discovery of unique features of bat immune systems which may have translational value as broad-spectrum antivirals, particularly if they evolved as a byproduct of bats' unique life history rather than through conventional co-evolutionary processes. Surprisingly, whether bats compared to other host groups suffer less disease from co-evolved viruses or from viruses generally has not been formally assessed. Here, synthesizing 86 years of experimental infections, involving 54 viruses, 85 host species, and over 5,600 animals, we document disease in bats following inoculation by taxonomically diverse viruses, including ones that are relatively benign in humans. The occurrence of overt disease, the likelihood of mortality, and the severity of disease in bats were indistinguishable from those experienced by rodents, another group associated with many zoonotic viruses. These patterns were consistent when considering only bat-associated viruses inoculated into bats and rodent-associated viruses inoculated into rodents and among inoculations which lacked shared co-evolutionary history. Instead, disease outcomes following infection were shaped by experimental design, viral host range, and evolutionary context. Unexceptional disease in bats from novel or co-evolved infections suggests that order-level host life history traits such as flight have inconsistent consequences for antiviral immunity and highlights the need to evaluate the functional properties of putatively unique features of bat immunity in vivo. While these results do not exclude the possibility of developing broader-acting or more potent antivirals from bat immune systems or diminish the potential value of mechanistic insights into bat immunity, they suggest that bat immune systems were shaped by conventional co-evolutionary processes rather than through unique circumstances that endow exceptional antiviral defenses.

The study of evolution in organisms with high mutation rates requires detailed data on the genomic composition of the population. Here we report on an innovative use of high-throughput sequencing technology combined with rapid experimental evolution that allowed us to follow the genetic diversification of four independent bacteriophage populations for 412 generations in extraordinary detail. One of our goals was to assess phylodynamic methods that use genetic information to infer key parameters of the population history. Because phylodynamic methods assume neutral evolution, we did not actively impose any selection pressures in our evolution experiment (in addition to those inherent in the bacterial cell environment). Tracing over 80'000 bacteriophage genomes, representing 884 distinct genotypes, we find that the patterns of viral diversification result in largely non-congruent genotype distributions, but also document multiple instances of parallel evolution. Unlike previous observations of parallelism in viral evolution, we do not just see the parallel evolution of mutations at single sites, but on the level of full-length genomes. Computer simulations that recapitulate our experiments in great detail show that this degree of parallelism is inconsistent with neutral evolution. We further show that the observed extent of parallel evolution biases phylodynamic analysis of migration rates, and wrongly estimates significant migration between the independent evolution lines. Our approach is applicable to many other viruses and paves the way to advanced population genetic investigations that aim to shed light on phenomena that relate to genetic linkage across the genome.

Goal-directed behavior requires sensory information to be transformed into motor commands, yet the precise temporal structure of communication between sensory and motor cortices during this process remains poorly understood. By simultaneously recording spiking activity from primary somatosensory cortex (S1) and secondary motor cortex (M2) in mice performing a tactile delayed go/no-go task, we identified a brief, stimulus-triggered communication window that predicted behavioral success. Time-shifted canonical correlation analysis revealed a sharp, feedforward surge in S1 → M2 coupling peaking at a short latency, as expected for a potentially direct transmission pathway. This transient interaction conveyed stimulus-selective information such that the S1 → M2 communication subspace aligned with stimulus-coding axes in both regions. In contrast, M2 → S1 feedback interactions were weaker and delayed. Brief optogenetic suppression of S1 reduced both M2 stimulus selectivity and behavioral discriminability, consistent with a functional role of the transient S1 → M2 coupling. These findings demonstrate that sensorimotor transformation is supported not by sustained linear coupling along the stimulus- or choice- axis, but by a short-lived and highly selective feedforward communication channel that rapidly transmits reliable sensory representations into motor-planning circuits.

Molecular profiling studies have mapped vascular alterations in Alzheimer's disease, but have not proven a role for them in pathology. Longitudinal studies are needed to link molecular and structural changes to vascular mechanics, hemodynamics, and tissue perfusion.

Bat sarbecoviruses differ in the range of mammalian ACE2 receptors they can use, complicating predictions of spillover risk. Two new studies in PLOS Biology link receptor breadth with antigenic relatedness and reveal conserved spike epitopes targetable by antibodies.

[This corrects the article DOI: 10.1371/journal.pbio.3002841.].

Sexual selection is a central force in evolutionary biology that has been shown to shape phenotypes and population dynamics in animals. While this selective force is increasingly recognized in flowering plants, theory predicts that anisogamy generates sex differences in the fitness benefits of acquiring additional mates-a pattern well supported in animals but with limited tests in plants. Plant studies rely solely on genetic parentage analyses to estimate mate numbers, thereby conflating performance in accessing mates with success in gamete fertilization. Pollinators add an ecological layer, as their behavior and abundance can influence competition for access to mates and their gametes. Here, we disentangle consecutive episodes of sexual selection in the hermaphroditic plant Brassica rapa by combining direct observations of Bombus terrestris movements with genetic paternity analyses in experimental populations, thus providing independent estimates of the observational number of mates acquired and realized fertilization success. Our approach identifies pollen competition for ovules as the primary arena for sexual selection in B. rapa. Competition for access to mates constitutes a secondary force and was found to be stronger in the male compared to the female sex function, as predicted by classic theory. Experimentally reduced pollinator abundance modulated the balance between pre- and post-pollination sexual selection, increasing the opportunity for selection on mate acquisition. Ignoring pollinator movements led to biased estimates of pre-pollination sexual selection. Our findings demonstrate that sexual selection in plants unfolds across multiple, sequential episodes shaped by ecological context.

Male mosquitoes locate females through strong and innate attraction to female flight sounds, the basis of mating in the world's deadliest animal. In contrast, females do not show any sound attraction behaviors. Despite being documented for almost a century, the molecular underpinnings of these behavioral dimorphisms remain unknown. Here, we found that by disrupting the male-specific isoform of fruitless (referred to as fruM) in Aedes aegypti, fruM mutant males show complete abolition of sound attraction behaviors, resulting in failure of mutant males to locate females for mating. We identified strong fruitless expression in control male ears, with the loss of FruM severely disrupting mutant male ability to amplify female flight sounds. fruM mutant male ears also propagate frequency-specific, sound-evoked electrical signals at about one-sixth the magnitude of control males, significantly reducing the amount of auditory information relayed to the brain. fruitless thus plays a significant role in determining proper male peripheral hearing function underlying mating. Transcriptomic analyses of mosquito ears identified essential hearing genes under the transcriptional influence of FruM via direct or indirect actions, thus shaping male-specific hearing cellular machineries that support male attraction to female flight sounds. Our work demonstrates that FruM commands male-specific hearing behaviors involved in mating by directly controlling the earliest stages of auditory organ performance, sound amplification and acoustic signal detection. Our findings show that FruM is essential for male-specific reproductive behaviors in mosquitoes.