eLife Assessment

This important study introduces an approach to discovering antibiotic resistance determinants by leveraging diverse susceptibility profiles among related mycobacterial species, with particular relevance to high-level resistance against natural product-derived antibiotics. The research provides convincing evidence for the role of ADP-ribosylation enzymes in rifamycin resistance among mycobacteria, whilst also demonstrating that antibiotic susceptibility is not correlated with growth rate or intracellular compound concentration. Although some broader claims require additional experimental support, this work lays a significant foundation for understanding the complexity of antibiotic resistance mechanisms in mycobacteria and opens new avenues for future antimicrobial research.

eLife Assessment

This important manuscript provides insights into the competition between Splicing Factor 1 (SF1) and Quaking (QKI) for binding at the ACUAA branch point sequence in a model intron, regulating exon inclusion. The study employs rigorous transcriptomic, proteomic, and reporter assays, with both mammalian cell culture and yeast models. Nevertheless, while the data are convincing, broadening the analysis to additional exons and narrowing the manuscript's title to better align with the experimental scope would strengthen the work.

eLife Assessment

This study presents an important finding on the role of telomeres in modulating interleukin-1 signaling and tumor immunity in TNBC. The evidence supporting these findings is solid, presented through comprehensive analyses including TNBC clinical samples, tumor-derived organoids, cancer cells, and xenografts. The work will be of broad interest to cell and medical biologists focusing on TNBC.

eLife Assessment

This study presents a valuable finding on how the sensorimotor control system deals with redundancy within our body, based on a novel bimanual task. The evidence supporting the authors' claims is convincing, as demonstrated over four different experiments. The work will be of interest to researchers from the motor control community and related fields, and further investigation into the interpretation of the findings could increase the generalisation of the study to a broader audience.

eLife Assessment

The contributions of ipsilateral cortical pathways to motor control are yet not fully understood. Here, the authors present important insights into their role in locomotion following unilateral spinal cord injury. Their data provide convincing evidence in rats that stimulation of ipsilateral motor cortex improves the injured side's ability to support weight and leads to improved locomotion, a result that may inspire new treatments for spinal or cerebral injuries.

eLife Assessment

This study provides convincing evidence for functional subpopulations of β-cells responsible for Ca2+ signal initiation and maintenance using novel three-dimensional light sheet microscopy imaging and analysis of pancreatic islets. The findings are important as they help decode the mechanistic underpinnings of islet calcium oscillations and the resulting pulsatile insulin secretion. The work will be of general interest to cell biologists and of particular interest to islet biologists.

eLife Assessment

The manuscript by Hills, et al. presents data that support multiple conclusions regarding the gene expression patterns of cells, especially chemosensory neurons. The evidence is largely solid, with transcriptomic analysis combined and validated by spatially resolved expression in tissue sections, but is incomplete in other ways with some claims not fully supported. This large-scale single-cell transcriptomics dataset is an important resource, alongside a thorough exploration of the molecular features of the different cell types within the mouse vomeronasal organ, including expression of chemosensory receptors.

eLife Assessment

This valuable study uses fluorescence lifetime imaging and steady-state and time-resolved transition metal ion FRET to characterize conformational transitions in the isolated cyclic nucleotide binding domain of a bacterial CNG channel. The data are compelling and support the authors' conclusions. The results advance the understanding of allosteric mechanisms in CNBD channels and have theoretical and practical implications for other studies of protein allostery. A limitation is that only the cytosolic fragments of the channel were studied.

eLife Assessment

The paper will be of broad interest to fungal biologists and fungal immunologists seeking to understand the biosynthesis of the fungal cell wall, in particular of ß-1,6-glucan synthesis and the importance of this so far understudied constituent of the cell wall for cell wall integrity and immune response. The study is of fundamental significance and adds structural clarity to the genetic, and biochemical basis of this difficult-to-analyze carbohydrate. It opens the potential for understanding its role in immune recognition and potentially as a drug target. Overall, the data is compelling, properly controlled and analyzed.

eLife Assessment

This valuable work presents the latest version of CTFFIND, which is the most popular software for determination of the contrast transfer function (CTF) in cryo-electron microscopy. CTFFIND5 estimates and considers acquisition geometry and sample thickness, which leads to improved CTF determination. The paper describes compelling evidence that CTFFIND5 finds better CTF parameters than previous methods, in particular for tilted samples (e.g. for cryo-electron tomography) or where thickness is an issue (e.g. cellular samples, or electron microscopy at low voltages).

eLife Assessment

This computational study integrates detailed electrophysiology and mechanical contraction predictions, which are often modeled separately. The findings of this important work are that abnormal ECGs that are associated with higher risk of sudden cardiac death are predicted to have almost no relationship with left ventricular ejection fraction, which is conventionally used as a risk factor for arrhythmia. The conclusions are based on compelling evidence for the need of incorporating additional risk factors for assessing post-myocardial infarction patients.

eLife Assessment

This work describes a circadian regulation in the expression of HERP, a regulator of endoplasmic reticulum calcium, in primary astrocytic cultures. This work is important because it highlights the potential importance of circadian rhythms in astrocytes, even though making a direct comparison between these rhythms in vitro and in vivo remains challenging. The technical approaches used in this work (RNA-seq, siRNA, Ca2+ imaging) are a solid support for data interpretation.

eLife Assessment

This valuable study provides solid support for the participation of the BMP-binding domain of MuSK, a tyrosine kinase mostly known for its role at the neuromuscular junction, in the maintenance and activation of muscle stem cells (SCs). These mononucleated cells, located between the muscle fiber basal lamina and its plasma membrane, are normally quiescent, but following muscle damage, become activated, proliferate, and mediate muscle regeneration. These cells are known to respond to a variety of signaling pathways, but this study makes the case for BMP acting via binding to MuSK in maintaining the quiescent state.

eLife Assessment

This valuable study reveals extensive binding of eukaryotic translation initiation factor 3 (eIF3) to the 3' untranslated regions (UTRs) of efficiently translated mRNAs in human pluripotent stem cell-derived neuronal progenitor cells. The authors provide solid evidence to support their conclusions, although this study may be enhanced by addressing potential biases of techniques employed to study eIF3:mRNA binding and providing additional mechanistic detail. This work will be of significant interest to researchers exploring post-transcriptional regulation of gene expression, including cellular, molecular, and developmental biologists, as well as biochemists.

eLife Assessment

The authors use single molecule imaging and in vivo loop-capture genomic approaches to investigate estrogen mediated enhancer-target gene activation in human cancer cells. These potentially important results suggest that ER-alpha can, in a temporal delay, activate a non-target gene TFF3, which is in proximity to the main target gene TFF1, even though the estrogen responsive enhancer does not loop with the TFF3 promoter. To explain these results, the authors invoke a transcriptional condensate model. The reviewers were split on the strength and interpretation of the evidence presented, which is considered incomplete at this stage. We encourage a revision which buttresses the findings with additional control experiments and careful consideration of alternative explanations and mathematical models. Further, the depth of the discussion on existing literature could be improved. This work will be of interest to those studying transcriptional gene regulation and hormone-aggravated cancers.

eLife Assessment

In this manuscript, the authors sought to elucidate mechanistic intricacies of inflammatory responses, with emphasis on T cell dysfunction, to S. aureus-induced pneumonia in the context of aging process using Terc deficient mice. Conceptually, the study is very interesting with a set of useful findings. Although some experimental approaches are appropriate, the work as shown in the revised manuscript remains significantly underpowered and the absence of rigorous controls make this study incomplete in support of its claims.

eLife Assessment

In this useful study, the authors present convincing evidence linking the enzyme D-alanine-D-alanine ligase (Ddl), crucial for cell wall fortification, to organic acid exposure in Staphylococcus aureus. While it's established that organic acids impede bacterial growth, the researchers reveal a novel coping mechanism where S. aureus maintains elevated levels of D-alanine, the substrate for Ddl, to counteract this inhibition. This discovery illuminates a bacterial strategy for organic acid tolerance, offering new insights for microbiologists and potentially informing future antimicrobial approaches.

eLife Assessment

The authors have developed a robust machine learning approach to predict radio sensitivity in patients with NPC based on a defined gene signature. Some key aspects of this signature have been validated in vitro using relevant cell lines which strengthens the conclusions of this important and convincing study. The publication will be of interest to clinicians working on this indication as well as a more broader readership made up of scientists working on radiation biology and those with a bioinformatics/machine learning background.

eLife Assessment

This study presents an important finding on durotaxis in various amoeboid cells that is independent of focal adhesions. The evidence supporting the authors' claims is compelling. The work will be of interest to cell biologists and biophysicists working on rigidity sensing, the cytoskeleton, and cell migration.

eLife Assessment

This study represents a potentially useful tool for extracting quantitative data from intravital microscopy directed at in vivo cancer models. In general, this is an area of interest as accessible non-proprietary tools are needed and some evidence of the tool's utility is provided. However, the work in its current form is incomplete as it is heavily reliant on proprietary software to segment, track, and correct the data. In addition, there are significant reservations regarding the methods used to produce statistics in the software, limiting its applicability and the potential advance over other approaches.

eLife Assessment

The study identifies the adhesion G-protein-coupled receptor A3 (ADGRA3) as a potential target for activating adaptive thermogenesis in white and brown adipose tissue, providing valuable information for scientists in the field of adipose tissue biology and metabolism. Although the authors have addressed some concerns raised by reviewers, the interpretations remain somewhat limited, and the work is deemed incomplete. The evidence supporting ADGRA3's role in thermogenesis is insufficient, necessitating more rigorous experiments to validate the receptor's relevance in adipose tissue. Additionally, the lack of experiments using primary cultures, despite feedback from multiple reviewers, highlights significant shortcomings.

eLife Assessment

This manuscript reports important data providing evidence that a 42 amino acid region of Rev7 is necessary and sufficient for interaction with the Rad50-Mre11-Xrs2 complex in budding yeast. The authors conclude that Rev7 inhibits the Rad50 ATPase and the Mre11 nuclease with the exception of ssDNA exonuclease activity. The convincing data largely support the conclusions, although the effect of Rev7 on homologous recombination is less well documented and the observed effect on resection is moderate. Specifically, the result that the Rev7 C-terminal truncation lacking the 42 amino acid region still suppresses homologous recombination is unexpected and unexplained.

eLife Assessment

The authors established a useful syndetome differentiation protocol from human induced pluripotent stem cells, guided by single-cell transcriptomic analysis. Their findings could significantly impact the field, particularly for patients needing tendon cell therapy. However, the evidence presented is currently incomplete, as the authors did not yet test the applicability of their protocol across multiple human induced pluripotent stem cell lines.

eLife Assessment

The study describes a link between beta-amyloid monomers, regulation of microglial activity and assembly of neocortex during development. It brings valuable findings that have theoretical and practical implications in the field of neuronal migration, neuronal ectopia and type II lissencephaly. Unfortunately, the evidence is incomplete and the manuscript would benefit from additional experiments to clarify the relationship between Ric8a and APP and bolster the findings.

eLife Assessment

This important study describes the function of Laminin y1-dependent basement membranes in development of the olfactory placode, including morphogenesis of the placode, boundary formation, and olfactory axonal pathfinding. The study uses elegant live imaging approaches and extensive quantitative analyses, combined with detailed mutant analyses to provide a compelling description of the role of Laminin in olfactory placode development. In addition to the contributions this study makes to understanding olfactory placode development, it will also be of broader interest to individuals studying extracellular matrix regulation of tissue morphogenesis, and neural development including neuronal pathfinding.

eLife Assessment

This important study suggests that the composition of the extracellular matrix in a mouse model of liver fibrosis changes depending on the cause of liver fibrosis. The data could be used as a foundation for future antifibrotic therapies. The strength of evidence is solid with respect to the use of animal models and proteomic analysis. The study provides a helpful inventory of proteins up or down-regulated, but functional analyses are limited and translational data are lacking.

eLife Assessment

This study provides valuable insights into the evolutionary histories and cellular infection responses of two Salmonella Dublin genotypes. While the evidence is compelling, a more phylogenetically diverse bacterial collection would enhance the findings. This research is relevant to scientists studying Salmonella and gastroenteritis-related pathogens.

eLife Assessment

Following up on their previous work, the authors investigated whether cell-to-cell transmission of HIV-1 activates the CARD8 inflammasome in macrophages. This is important given that inflammasome activation in myeloid cells triggers proinflammatory cytokine release. The data are solid and support the idea that CARD8 is activated by the viral protease and promotes inflammation. However, time-course analyses in primary T cells and macrophages and further information on the specific inflammasome involved would further increase the significance of the study.

eLife Assessment

This valuable study investigates prey capture by archer fish, showing that even though the visuomotor behavior unfolds very rapidly (within 40-70 ms), it is not hardwired; it can adapt to different simulated physics and different prey shapes. Although there was agreement that the model system, experimental design, and main hypothesis are certainly interesting, opinions were divided on whether the evidence supporting the central claims is incomplete. A more rigorous definition and assessment of "reflex speed", more detailed evidence of stimulus control, and a more detailed analysis of individual subjects could potentially increase confidence in the main conclusions.

eLife Assessment

This study provides evidence that cerebellar projections to the thalamus are required for learning and execution of motor skills in the accelerating rotarod task. This important study adds to a growing body of literature on the interactions between the cerebellum, motor cortex, and basal ganglia during motor learning. The data presentation is generally sound, especially the main observations, with some limitations in describing the statistical methods and a lack of support for two segregated cerebello-thalamic pathways, which is incomplete in supporting the overall claim.

eLife Assessment

This important study advances our understanding of the way neurons in the auditory cortex of mice respond to unpredictable sounds. Through the use of state-of-the-art recording methods, compelling evidence is provided that responses to local and global violations in sound sequences are prediction errors and not simply the consequence of stimulus-specific adaptation. Although the cell-type-specific results are intriguing, further work is needed to establish their reliability.

eLife Assessment

This important study partially fills the gap in the knowledge of olfaction at the level of the Anterior Olfactory Nucleus (AON) and Piriform Cortex with functional magnetic resonance imaging, electrophysiology, and modeling. The methods used are convincing. Some of the findings confirm ongoing hypotheses, such as the behavioral importance of AON for odor source discrimination. Other results shed light on the dynamics of the connection between the olfactory system and the rest of the brain.

eLife Assessment

This important collection of over 800 new cell type-specific driver lines will be an invaluable resource for researchers studying associative learning in Drosophila. Thoroughly characterized and well documented, this collection will permit researchers to selectively target neurons that deliver information to, or receive it from, the memory center of the fly brain called the Mushroom Body. Given the wealth of new drivers and the genetic access they provide to over 300 cell types, this compelling work will be of interest not only to researchers studying the mechanisms of associative learning but more generally to those dissecting sensorimotor circuits in the fly nervous system.

eLife Assessment

This study compiles a wide range of results on the connectivity, stimulus selectivity, and potential role of the claustrum in sensory behavior. While most of the connectivity results confirm earlier studies, this valuable work provides incomplete evidence that the claustrum responds to multimodal stimuli and that local connectivity is reduced across cells that have similar long-range connectivity. The conclusions drawn from the behavioral results are weakened by the animals' poor performance on the designed task. This study has the potential to be of interest to neuroscientists.

eLife Assessment

This valuable study investigates the relationship between neuronal dynamics in the thalamus and brain state modulation. The claims that a specific channel is a critical player in the regulation of brain-states and ethanol-resistance in mice are supported by convincing evidence. The work will be of interest to systems neuroscientists interested in brain dynamics and behavioural states.

eLife Assessment

This important study investigates how AD(H)D affects attention using neural and physiological measures in a Virtual Reality (VR) environment. Solid evidence is provided that individuals diagnosed with AD(H)D differ from control participants in both the encoding of the target sound and the encoding of acoustic interference. The VR paradigm here can potentially bridge lab experiments and real-life experiments. However, the reviewers identified a few potential technical issues that will need to be verified and discussed.

eLife Assessment

This study describes a new analysis strategy to compare active neurons during behavioral tasks across the brain. This is significant because analysing how different brain areas are active during behavior requires better methods. The evidence provided in support of the method is solid. Although useful now, the work may increase its significance following appropriate revisions.

eLife Assessment

This study presents an important application of high-content image-based morphological profiling to quantitatively and systematically characterize induced pluripotent stem cell-derived mixed neural cultures cell type compositions. Compelling evidence through rigorous experimental and computational validations support new potential applications of this cheap and simple assay.

eLife Assessment

This study provides a valuable description of subtypes of V1 neurons, including birthdates and connections to motor neurons. V1 neurons are one of the main groups of inhibitory neurons in the spinal cord. The methods of data collection and analysis are convincing. This work will interest developmental biologists and neuroscientists working on spinal circuits.

eLife Assessment

This important study investigates the contribution of cytosolic S100A/8 to neutrophil migration to inflamed tissues. The authors provide convincing evidence for how the loss of cytosolic S100A/8 specifically affects the ability of neutrophils to crawl and subsequently adhere under shear stress. This study will be of interest in fields where inflammation is implicated, such as autoimmunity or sepsis.

eLife Assessment

This valuable study reports the existence of specific spike-timing dependent synaptic plasticity processes at two excitatory synapses of the dentate gyrus granule cells. These synapses link the entorhinal cortex and the dentate gyrus but via different circuits. With state-of-the-art patch-clamp electrophysiological analysis, the authors provide convincing information on the molecular mechanisms underlying these 2 forms of synaptic plasticity showing a critical role for astrocytes in both alongside some features distinctive to each pathway. These results will be of interest to neuroscientists as they uncover detailed plasticity mechanisms involving the hippocampus.

eLife Assessment

This study is deemed to be an important work that carefully deconstructs multi-faceted conditioned fear behavior in mice. The well-controlled experiments provide convincing data that will be of interest to other researchers in the field.

eLife Assessment

This valuable modeling study explores how biophysical properties of different interneuron subtypes in the basolateral amygdala (BLA) enable production of oscillations that facilitate functions such as spike-timing-dependent plasticity. Simulated networks provide solid evidence that highlights the importance of interactions between interneurons for some forms of spike-timing dependent plasticity. This work will likely be of interest to investigators studying interactions among interneurons, rhythms in the amygdala, and mechanisms of plasticity thought to underlie associative learning.

eLife Assessment

This important study demonstrated that ablation of astrocytes in the lumbar spinal cord not only reduced neuropathic pain but also caused microglia activation. The findings presented add considerable value to the current understanding of the role of astrocyte elimination in neuropathic pain, offering convincing evidence that supports existing hypotheses and insights into the interactions between astrocytes and microglial cells, likely through IFN-mediated mechanisms

eLife Assessment

The study is valuable to the field, introducing a new model to test BM-periosteal stem cell function in vivo. The authors' findings suggested that periosteal stem cells are linked to hematopoietic regeneration. More comparisons with the conventional model and direct examination of periosteal stem cell factors in hematopoietic regeneration are missing. The observations are solid, however, the limitations in their experimental model made the overall impact incomplete; there is potential for improvements to be made in this area.

eLife Assessment

This important study aimed to identify how chronic heat exposure affects subsequent behavior and brain function. This work positively expands the field of thermoregulation. The data were collected using a myriad of next-generation approaches, including extensive behavior testing, thermal monitoring, electrophysiology, circuit mapping, and manipulations. As a result the strength of evidence is mostly solid, however a few weaknesses drove the some of the conclusions to be incompletely supported. These largely circle around the question of how unique these effects are to thermal stress (as opposed to other forms of stress), a lack of statistical analyses and rigor in some of the experiments and figures, and the specificity of the POA-pPVT pathway compared to other inputs to the PVT in the control of observed effects.

eLife Assessment

This valuable manuscript reports a large-scale, data-driven, biophysically detailed model of the non-barrel primary somatosensory cortex and generates numerous predictions that can further our understanding of how the multiscale organization of the cortex shapes neural activity. While the approach is solid, many of the findings are obtained using a much smaller portion of the model, which, together with the broad scope of the work, makes the narrative somewhat confusing and the strength of findings not entirely clear.

eLife Assessment

This study provides abundant valuable scRNA-Seq data that profiles fibroblasts involved in myocardium and coronary vasculature development. However, the evidence supporting the authors' claims is currently incomplete. The inclusion of additional citations, more in-depth discussions, and further analyses or experiments to validate the scRNA-Seq data would have significantly strengthened the study. Nonetheless, the scRNA-Seq expression data will be a resource that is of value to researchers in the field.

eLife Assessment

This study presents two main findings regarding HIV-1 genomic integration. The first, based on convincing evidence in primary cell models, is that HIV-1 induces R loop formation, though the viral driver of this process remains undefined. The second, based on model cell systems with limited physiological relevance to HIV-1, is that a portion of HIV-1 genomes integrates in the vicinity of where R loops form. This finding has the potential to offer fundamental insight into HIV-1 integration, but the strength of the presented evidence was viewed as incomplete and needing additional validation by more direct experimental methods in order to understand what the mechanistic relationship between the formation of R loops and HIV-1 integration is.

eLife Assessment

This useful study presents a biologically realistic, large-scale cortical model of the rat's non-barrel somatosensory cortex, investigating synaptic plasticity of excitatory connections under varying patterns of external activations and characterizing relations between network architecture and plasticity outcomes. While the model demonstrates several interesting phenomena, the results are less explanatory of causal relationships and more observational in nature; hence the evidence supporting the main conclusions remains incomplete.

eLife Assessment

This important study explores the interplay between gene dosage and gene mutations in the evolution of antibiotic resistance. The authors provide solid evidence to connect proteostasis with gene duplication during experimental evolution in a model system. If the experiments are found to be rigorous and reproducible, then this paper will be of high interest to other researchers studying antibiotic resistance, proteostasis, and bacterial evolution.

eLife Assessment

This valuable work explores the timely idea that aperiodic activity in human electrophysiology recordings shows changes in response to task events, which may be relevant for performance, and that these changes could be misinterpreted as oscillatory changes. While it is a timely and interesting topic in principle, in the present form, the analytic approach is incomplete. Further, the data offer inadequate support for the conclusions related to theta without demonstrations that the task evokes theta power. Impressions were split, but there was consensus that the Discussion should be tempered and that revisions would improve the manuscript.

eLife Assessment

This important study showing that sleep deprivation increases functional synapses while depleting silent synapses supports previous findings that excitatory signaling increases during wakefulness. This manuscript focuses in particular on AMPA/NMDA ratios. An interesting, although speculative, aspect of the manuscript is the inclusion of a model for the accumulation of sleep need that is based upon the MEF2C transcription factor but also links to the sleep-regulating SIK3-HDAC4/5 pathway. The authors have clarified some questions raised in the previous review, but the evidence for major claims was still found to be incomplete, requiring additional experimentation.

eLife Assessment

This useful study sheds light on the species-specific nature of sperm-oocyte interactions by examining sperm binding and penetration of the zona pellucida across various mammalian species. While the evidence remains incomplete, the authors propose that two distinct mechanisms drive mammalian sperm-oocyte recognition and penetration: a specific, zona pellucida (ZP)-mediated mechanism, and a non-specific, oviductal glycoprotein 1 (OVGP1)-mediated mechanism. Upon revision, this study would offer insights to reproductive biologists, potentially improving porcine in vitro fertilization (IVF) - which is particularly susceptible to polyspermy - and enhancing sperm selection processes in human IVF, ultimately leading to better outcomes in assisted reproduction techniques.

eLife Assessment

This useful study shows how genetic variation is associated with fecundity following a period of reproductive diapause in female Drosophila. The work identifies the olfactory system as central to successful diapause with associated changes in longevity and fecundity. While the methods used are solid, a limitation of the study, as of any other laboratory-based investigation is the challenge of demonstrating how well measures for fitness related to diapause and its recovery correlates with realities encountered during development in the wild.

eLife Assessment

This study presents a useful investigation of the use of small, de novo-designed protein binding domains (mini-binders) against the Spike protein of SARS-CoV-2 and EGFR, as ligand binding domains on two classes of synthetic receptors, second-generation synNotch (SNIPR) and CAR. The methods and evidence supporting the focused claims are solid. This work will be of interest to synthetic biologists and cell engineers as a starting point to map out the rules for receptor engineering based on mini-binders and ultimately to advance them in biomedical applications.

eLife Assessment

The authors developed a method to allow a hypothermic agent, neurotensin, to cross the blood-brain barrier so it could potentially protect the brain from seizures and the adverse effects of seizures. The work is important because it is known that cooling the brain can protect it but developing a therapeutic approach based on that knowledge has not been done. The paper is well presented and the data are convincing.

eLife Assessment

Fallah et al carefully dissect projections from substantia nigra pars reticulata (SNr) and the globus pallidus externa (GPe) – two key basal ganglia nuclei – to the pedunculopontine nucleus (PPN), a brainstem nucleus that has a central role in motor control. They consider inputs from these two areas onto 3 types of downstream PPN neurons – GABAergic, glutamatergic, and cholinergic neurons – and carefully map connectivity along the rostrocaudal axis of the PPN. Overall, this valuable study provided convincing data on PPN connectivity with two key input structures that will provide a basis for further understanding PPN function.

eLife Assessment

This useful manuscript reports on a new mouse model for LAMA2-MD, a rare but very severe congenital muscular dystrophy; the knockout mice were generated by removing exon3 in the Lama2 gene, which results in a frameshift in exon4 and a premature stop codon. These animals lack any laminin-alpha2 protein and confirm results from previous Lama2 knockout models. Additionally, this study includes transcriptomics data that might be a good resource for the field. However, the experimental evidence supporting the main claims of the manuscript is incomplete, citations of previous Lama2 null mice studies are lacking, and both data presentation and interpretation need improvement.

eLife Assessment

This study makes an important contribution by characterizing the role of the exocyst in secretory granule exocytosis in the Drosophila larval salivary gland. The results are solid and lead to the novel interpretation that the exocyst participates not only in exocytosis, but also in earlier steps of secretory granule biogenesis and maturation. However, the authors are urged to provide additional proof that the exocyst subunit knockdowns were effective and to acknowledge the possibility that inactivation of an essential exocytosis component could indirectly affect other parts of the secretory pathway.

eLife Assessment

This fundamental study substantially advances our understanding of how habitat fragmentation and climate change jointly influence bird community thermophilization in a fragmented island system. The authors provide convincing evidence using appropriate and validated methodologies to examine how island area and isolation affect the colonization of warm-adapted species and the extinction of cold-adapted species. While minor clarifications regarding the definition of fragmentation could further enhance the presentation, the study is of high interest to ecologists and conservation biologists, as it provides insight into how ecosystems and communities respond to climate change.

eLife assessment

This proof-of-concept study focuses on an A->G DNA base editing strategy that converts CAG repeats to CAA repeats in the human HTT gene, which causes Huntington's disease (HD). These studies are conducted in human HEK293 cells engineered with a 51 CAG canonical repeat and in HD knock-in mice harboring 105+ CAG repeats. The findings of this study are valuable for the HD field, applying state-of-the-art techniques. However, the key experiments have yet to be performed in neuronal systems or brains of these mice: actual disease-rectifying effects relevant to patients have yet to observed, leaving the work incomplete.

eLife assessment

This study presents a useful examination of the prevalence of interactions between amino acids from different periods of Earth's history and coenzymes. While the premise of this work is well founded, the data lend themselves to alternative interpretations, suggesting that the main conclusions might be incompletely supported by the findings. The work would benefit from the inclusion of additional supplementary data and further analysis. This manuscript would be of interest to evolutionary biologists and biophysicists.

eLife assessment

This is a valuable study of the mechanisms of microtubule organization in pancreatic islet beta cells that enable optimal insulin secretion. Using a combination of live imaging and photo-kinetic assays in an in vitro culture system, the authors provide solid evidence to demonstrate that kinesin-1-mediated microtubule sliding, which has previously been known from neurons and embryos, is essential for establishing the sub-membranous microtubule band in response to glucose levels in beta cells. The inclusion of an animal model or primary cells, as well as data on the physiological relevance of the finding, would have strengthened the study. The work will be of interest to cell biologists studying cytoskeletal dynamics and organelle trafficking and to translational biologists working on diabetes.

eLife Assessment

In this valuable paper, the authors created a reporter mouse line in which the Axon Initial Segment (AIS) is intrinsically labeled by an ankyrin-G-GFP fusion protein activated by Cre recombinase, tagging the native Ank3 gene. Using confocal, superresolution, and two-photon microscopy as well as whole-cell patch-clamp recordings in vitro, ex vivo, and in vivo, the authors convincingly document that the subcellular scaffold of the AIS and electrophysiological parameters of labeled cells remain unchanged. They further uncover rapid AIS remodeling following increased network activity in this model system, as well as highly reproducible in vivo labeling of AIS over weeks.

eLife Assessment

This in several parts valuable study confirms the roles of Dact1 and Dact2, two factors involved in Wnt signaling, during zebrafish gastrulation and demonstrates their genetic interactions with other Wnt components to modulate craniofacial morphologies. Unfortunately, there are several limitations associated with the study, making it challenging to distinguish the primary and secondary effects of each factor, and their roles in craniofacial morphogenesis. The findings of a new potential target of dact1/2-mediated Wnt signaling are potentially of value; however, experimental evidence supporting their functional significance remains incomplete due to inconsistent results and limitations inherent to the overexpression approach.

eLife Assessment

This important work presents a consolidated overview of the NeuroML2 open community standard and provides convincing evidence for its central role within a broader software ecosystem for the development of neuronal models that are open, shareable, reproducible, and interoperable. A major strength of the work is the continued development over more than two decades to establish, maintain, and adapt this standard to meet the evolving needs of the field. This work is of broad interest to the sub-cellular, cellular, computational, and systems neuroscience communities undertaking studies involving theory, modeling, and simulation.

eLife Assessment

This useful study uses an intranasal mouse infection model with Streptococcus suis, a gram-positive bacterial pathogen that causes severe losses in pigs around the world. The manuscript provides insights that the capsular polysaccharide, one of the virulence factors of this pathogen, contributes to tissue dissemination and neurotropism in the host. However, the evidence is currently incomplete, and further experiments and careful interpretation of the current results and methods used are necessary to support the conclusions of the manuscript.

eLife Assessment

A regression discontinuity analysis finds essentially no effect of 1 additional year of secondary education on brain structure in adulthood. This is a valuable finding that adds to the literature on the impact of education on brain health. The evidence presented is solid, with strengths including methodological novelty as well as principled study design; the impact is, however, limited as the manipulated variable only relates to a single additional year of education (remaining in education to 15 vs 16 years of age). The interpretation is further missing discussion of the healthy volunteer bias of the UK Biobank sample, amplified in the imaging extension.

eLife Assessment

This is an important study examining the role of conserved PCH-2 protein at different stages of C. elegans meiosis. The authors use elegant molecular genetic approaches to provide convincing evidence to support their claims. The work will be of interest to scientists studying meiosis, DNA recombination, and chromosome segregation.

eLife Assessment

The manuscript provides important new insights into the mechanisms of statistical learning in early human development, showing that statistical learning in neonates occurs robustly and is not limited to linguistic features but occurs across different domains. The evidence is convincing, although an additional experimental manipulation with conflicting linguistic and non-linguistic information as well as further discussion about the linguistic vs non-linguistic nature of the stimulus materials would have strengthened the manuscript. The findings are highly relevant for researchers working in several domains, including developmental cognitive neuroscience, developmental psychology, linguistics, and speech pathology.

eLife Assessment

This paper contains valuable ideas for methodology concerned with the identification of genes associated with disease prognosis in a broad range of cancers. However, there are concerns that the statistical properties of MEMORY are incompletely investigated and described. Further, more precise details about the implementation of the method would increase the replicability of the findings by other researchers.

eLife Assessment

The study is important - not only for its comprehensive transcriptomic analysis of the developmental trajectory of syncytiotrophoblasts (STBs), but also for its comparative evaluation of primary human placental tissues and two human trophoblast organoid models. The study highlights the utility of these organoid models in advancing research on human STB biology. The conclusions of this work are supported by compelling analyses and experimental evidence.

eLife Assessment

This valuable study uses robust time-dependent microscopy assays to show that during HIV-1 infection, the viral accessory protein Vif causes cell cycle arrest during metaphase and not G2/M as previously thought. The conclusions are convincing in the context of the immortalized cellular models used, and they serve as a starting point to determine whether Vif-dependent regulation of the cell cycle modulates HIV-1 replication and pathogenesis in more physiologically relevant primary cells or in vivo.

eLife Assessment

This important work investigates the mechanism that underlies the switch between feeding and mating behaviors in the oriental fruit fly, Bactrocera dorsalis. Using a variety of approaches, the authors show that this switch is mediated by the neuropeptide, sulfakinin, acting peripherally through the sulfakinin receptor 1 to regulate the expression of antennal odorant receptors. The evidence is solid in support of the hypothesis that sulfakinin signaling mediates changes in the periphery, although additional experimental details would strengthen these claims.

eLife Assessment

Shen et al. present a computational account of individual differences in mouse exploration when faced with a novel object in an open field from a previously published study (Akiti et al.) that relates subject-specific intrinsic exploration and caution about potential hazards to the spectrum of behaviors observed in this setting. Overall, this computational study is an important contribution that leverages a very general modeling framework (a Bayes Adaptive Markov Decision Process) to quantify and interrogate distinct drivers of exploratory behavior under potential threat. Given their assumptions, the modeling results are convincing: the authors are able to describe a substantial amount of the behavioral features and idiosyncracies in this dataset, and their model affords a normative interpretation related to inherent risk aversion and predation hazard "flexibility" of individual animals and should be of broad interest to researchers working to understand open-ended exploratory behaviors.

eLife Assessment

This useful study examines the function of the rnc gene, which encodes the RNase III ribonuclease, as it relates to virulence of Salmonella Enteritidis. The authors demonstrate that the rnc gene is markedly upregulated in strains proposed to exhibit high virulence and that the product of the rnc gene promotes the expression of SodA, which contributes to the survival of Salmonella Enteritidis in the face of oxidative stress. The study also suggests that elevated levels of rnc gene expression assist Salmonella Enteritidis in evading immune responses by diminishing the presence of accumulated double-stranded RNA (dsRNA), although the evidence substantiating this and the above assertions remains incomplete.

eLife Assessment

The authors propose that positive biodiversity-ecosystem functioning relationships found in experiments have been exaggerated because commonly used statistical analyses are flawed. To remedy this, a new type of analysis based on a concept of "partial density monoculture yield" is proposed. However, the presented concept and analysis methods are not reproducibly described, do not appear to be complete, and are inadequate for hypothesis testing. The reviewers found that the authors misinterpret current research in the field and made limited efforts to understand or address the reviewer comments on a previous version of the study.

eLife Assessment

The authors present an important theoretical framework that describes the interplay between liquid-liquid phase separation and protein aggregation within a mean-field model. This work will be of high interest to the biophysics and molecular biology communities, as it will help understand and analyse assembly within biomolecular condensates in cells or in-vitro. Major strengths of this convincing work are the consideration of aggregates with various dimensionality and the possibility for protein gelation.

eLife Assessment

This valuable study provides an experimental paradigm and state-of-the-art analysis method for studying the existence of call types and transition differences among Mongolian gerbil families in a naturalistic environment. The analyses are convincing, with a thorough treatment of the acoustic data and a demonstration of the robustness of the observed effect across days. The work will likely be of interest to the auditory neuroscience and neuroethology communities.

eLife Assessment

This valuable study investigates evolutionary aspects around a single amino acid polymorphism, known to be under long-term balancing selection, in an immune peptide of Drosophila melanogaster. Using alleles with different substitutions, the investigators demonstrate that while one allele provides better survival after systemic infections by a bacterial pathogen, the alternative allele endows its carriers with a longer lifespan under certain conditions. The authors suggest that these contrasting fitness effects of the two alleles contribute to balancing their long-term evolutionary fate. While the work is very interesting, the strength of the provided evidence is still incomplete, and the study would benefit from more rigorous approaches.

eLife Assessment

This manuscript addresses infections of the parasite Taenia solium, which causes neurocysticercosis (NCC). NCC is a common parasitic infection that leads to severe neurological problems. It is a major cause of epilepsy, but little is known about how the infection causes epilepsy. The authors used neuronal recordings, imaging of calcium transients in neurons, and glutamate-sensing fluorescent reporters. A strength of the paper is the use of both rodent and human preparations. The results provide convincing evidence that the larvae secrete glutamate and this depolarizes neurons. Although it is still uncertain exactly how epilepsy is triggered, the results suggest that glutamate release contributes. Therefore, the paper is a fundamental step towards understanding how Taenia solium infection leads to epilepsy.

eLife Assessment

This study presents a valuable new method for probing the DNA and proteins associated with targeted genomic elements in cells. The authors present solid evidence that the method can map DNA-DNA interactions for individual loci and can detect enriched proteins at repetitive DNA loci such as telomeres, but benchmarks of the method's resolution and specificity remain incomplete. The methodological details of this study will be of particular interest and utility to chromatin biologists.

eLife Assessment

This valuable paper describes the crystal structure of a complex of Sld3-Cdc45-binding domain (CBD) with Cdc45, which is essential for the assembly of an active Cdc45- MCM-GINS (CMG) double hexamers at the replication origin. Although the results shown in the paper are of interest to researchers in DNA replication and genome stability, the biochemical analysis of protein-protein interaction and DNA binding is incomplete, and the paper needs additional data and revised discussion.

eLife Assessment

The aim of this useful study is to investigate the role of semilunar granule cells on memory engrams in the dentate gyrus. Which cells get recruited during contextual memory processing is a timely and significant question. However, evidence for the study's major conclusions is currently incomplete due to caveats in study design, technical limitations, and missing controls.

eLife Assessment

This study offers a valuable genomic dataset, analyses, and functional studies on gonadal sex determination and development. The work addresses long-standing questions regarding the role of the Drosophila sex determination hierarchy, sex chromosomes, and the interaction between the sex determination hierarchy and sex chromosome composition in gonad development. Although this convincing work has been conducted rigorously, the authors missed some key opportunities in their analysis.

eLife Assessment

The study presents important findings that reveal SEPHS2 and VPS37C as new potential drug targets for dasatinib and hydroxychloroquine respectively in addition to confirming known targets of these drugs. The evidence provided is solid, however, some of the claims are not fully supported by the data. To enhance the conclusions and readability, the writing clarity, data analysis and justification of experimental design rationale need to be worked on to enhance the study's interest among chemical biologists, biochemists, and scientists in drug discovery.

eLife Assessment

This valuable paper shows image correlation spectroscopy (ICS) as a new tool to analyze the clustering of proteins involved in DNA damage response (DDR). The solid evidence presented demonstrates that this method is more sensitive than traditional focus counting, although some of the claims require further contextualization. This new method provides an alternative tool to analyze immuno-stained focus for researchers in the fields of DDR and cell biology.

eLife Assessment

This important study provides a comprehensive analysis of how substitutions within the catalytic domain of the tyrosine kinase Met affect its sensitivity to inhibition by ATP-competitive, small molecule inhibitors and provides a mechanistic framework for understanding drug resistance. The evidence supporting the authors' claims is convincing, the data sets are comprehensive, and the analyses are rigorous. This work will be of broad interest to biochemists, structural biologists, and medicinal chemists.

eLife Assessment

This important study leverages an impressive and comprehensive longitudinal 16S microbiome dataset from baboons to provide insights regarding the use of a microbiome-based clock to predict biological age, with solid evidence for age-associated microbiome features and environmental and social variables that impact microbiome aging. This study of microbiomes as markers of host age will be relevant to a broad range of researchers, especially those interested in alternatives to measuring biological aging.

eLife Assessment

This is a valuable report of tracheal terminal cells (TTCs) in Drosophila being immune privileged. The authors demonstrated that TTCs lack the expression of membrane-associated peptidoglycan recognition receptor PGRP-LC, which protects these cells from activating immune pathway or JNK-mediated cell death to maintain TTC homeostasis. While genetic experiments using RNAi and overexpression are mostly convincing, the data on the expression of PGRP-LCx and cell death phenotypes following immune activation are currently incomplete. The work will be of interest to researchers in innate immunity across various model systems.

eLife Assessment

This useful study presents the first detailed and comprehensive description of brain sulcus anatomy of a range of carnivoran species based on a robust manual labeling model allowing species comparisons. Although the database is recognized and the method for reconstructing cortical surfaces is convincing, the evidence supporting the conclusions is incomplete due to the lack of appropriate quantitative measurements and analyses. Considering additional specimens to assess intraspecies variations, as well as exploring the functional correlates of interspecies differences would increase the scope of the study. Setting an instructive foundation for comparative anatomy, this study will be of interest to neuroscientists and neuroimaging researchers interested in that field, as well as in brain morphology and sulcal patterns, their phylogeny, and ontogeny in relation to functional development and behaviour.

eLife Assessment

This important paper by Lechler and colleagues describes the transcriptomic signature and fate of intermediate cells (ICs), a transient and poorly defined embryonic cell type in the skin. The paper convincingly shows through lineage tracing that ICs are granular and not spinous cell precursors, and through ectopic expression in vivo, that cell contractility, a mechanical feature of ICs, lies upstream of differentiation.

eLife Assessment

This valuable study shows that eliminating a large portion of the principal neurons in the mammalian olfactory bulb does not affect the initial establishment of the circuit but has an impact on its maintenance. The strength of the paper is that the anatomical changes induced by genetic ablation of neurons are clear-cut. There is solid support for the findings, with a description of the structural and behavioral effects of ablating the majority of M/T neurons.

eLife Assessment

This study presents a valuable finding on a potential signaling pathway responsible for the direct effects of nicotine on intestinal stem cell growth and tumorigenesis.  The evidence supporting the claims of the authors is solid. This research will be of interest to medical biologists specializing in intestinal tumors.

eLife Assessment

This study provides an important re-evaluation of modality-specific information processing in the thalamus of trained mice. Using an elegant task design that probes competing tactile and visual stimuli, the authors present compelling evidence that behavioral training reshapes the sensitivity of higher-order thalamic nuclei. Despite the powerful task design and the significance of the main findings, the origin of the cross-modal responses remains an open question and requires future investigation.

eLife Assessment

This paper addresses an important topic (normative trajectory modelling), seeking to provide a method aiming to accurately reflect the individual deviation of longitudinal/temporal change compared to the normal temporal change characterized based on a pre-trained population normative model. The evidence provided for the new methods is, however, incomplete, with the simulations validating the method needing to be extended.

eLife Assessment

This article presents valuable findings on the impact of climate change on odonates, integrating phenological and range shifts to broaden our understanding of biodiversity change. The study leverages extensive natural history data, offering a combined analysis of temporal trends in phenology and distribution and their potential drivers. The support for the findings is solid, though additional clarification regarding the methods and alternative sensitivity analyses could make the conclusions stronger.

eLife Assessment

This study poses an important step forward in understanding the brain-network embedding of beta oscillations. The study advances our circuit-level understanding of the pathophysiology associated with dopaminergic alterations in psychiatric or neurological disorders. The study provides compelling evidence that beta oscillations across the neocortex and basal ganglia map onto shared functional and structural networks that show significant positive correlations with dopamine receptors.

eLife Assessment

This important study substantially advances our understanding of nocturnal animal navigation and the ways that animals use polarized light. The evidence supporting the conclusions is convincing, with elegant behavioural experiments in actively navigating ants. The work will be of interest to biologists working on animal navigation or sensory ecology.

eLife Assessment

This important study presents a statistical framework for the analysis of photometry signals and provides an open-source implementation. The evidence supporting the benefits of the presented functional mixed-effect modeling analysis as opposed to 1) summary statistics and 2) other pointwise regression models is convincing with a thorough comparison with other methods and datasets. This work will be of great interest to researchers using not only fiber photometry, but other time-series data such as calcium imaging or electrophysiology data, and wanting to implement trial-by-trial temporal analysis, taking also into account variability within the dataset.

eLife Assessment

This valuable study is a companion to a paper introducing a theoretical framework and methodology for identifying Cancer Driving Nucleotides (CDNs). The evidence that recurrent SNVs or CDNs are common in true cancer driver genes is convincing, with more limited evidence that many more undiscovered cancer driver mutations will have CDNs, and that this approach could identify these undiscovered driver genes with about 100,000 samples.

eLife Assessment

This important paper introduces a theoretical framework and methodology for identifying Cancer Driving Nucleotides (CDNs), primarily based on single nucleotide variant (SNV) frequencies. A variety of solid approaches indicate that a mutation recurring three or more times is more likely to reflect selection rather than being the consequence of a mutation hotspot. The method is rigorously quantitative, though the requirement for larger datasets to fully identify all CDNs remains a noted limitation. The work will be of broad interest to cancer geneticists and evolutionary biologists.

eLife Assessment

The authors proposed an important novel deep-learning framework to estimate posterior distributions of tissue microstructure parameters. The method shows superior performance to conventional Bayesian approaches and there is convincing evidence for generalizing the method to use data from different protocol acquisitions and work with models of varying complexity.

eLife Assessment

The manuscript reports a valuable finding on dopamine receptor-mediated regulation, the firing of striatal cholinergic interneurons in both healthy and dyskinesia states, identifying that Kv1 channels play a key role in the burst-dependent pause. The study presents solid experimental data, and provides additional mechanistic insights into how burst activity in SCINs leads to a subsequent pause, highlighting the involvement of D1/D5 receptors. This work will be of interest to researchers studying the pathological mechanisms of Parkinson's disease.

eLife Assessment

This study introduces a novel method for estimating spatial spectra from irregularly sampled intracranial EEG data, revealing cortical activity across all spatial frequencies, which supports the global and integrated nature of cortical dynamics. The study showcases important technical innovations and rigorous analyses, including tests to rule out potential confounds; however, the lack of comprehensive theoretical justification and assumptions about phase consistency across time points renders the strength of evidence incomplete. The dominance of low spatial frequencies in cortical phase dynamics continues to be of importance, and further elaboration on the interpretation and justification of the results would strengthen the link between evidence and conclusions.

eLife Assessment

The authors show MRI relaxation time changes that are claimed to originate from cell membrane potential changes. This would be very important if true because it may provide a mechanism whereby membrane potential changes could be inferred noninvasively. However, the membrane potential manipulations applied here will induce cell swelling, and cell swelling has been previously shown to affect relaxation time. Therefore, the claim that the relaxation time changes observed in this manuscript are due to cell membrane potential changes is inadequately supported.

eLife Assessment

The authors have provided a valuable addition to the literature on large-scale electrophysiological experiments across many labs. The evidence that the authors provided was incomplete - while some comparisons with analyses outside of the manuscript's approaches were provided, a more complete manuscript would have compared with alternative standardized analyses. In particular, alternative spike sorting metrics and the alternative of GLM-based analysis of data would have made the interpretation of the results clearer.

eLife Assessment

In this paper, Seon and Chung investigate changes in own risk-taking behavior, when they are being observed by a "risky" or "safe" player. Using computational modeling and model-informed fMRI, the authors present solid evidence that participants adjust their choice congruent with the other player's type (either risky or safe). The conclusions of the paper are an important contribution to the field of social decision-making as they show a differentiated adjustment of choices and not just a universally riskier choice behavior when being observed as has been claimed in previous studies.

eLife Assessment

This useful study reports on the impact of antibiotic pressure on the genomic stability of the mc2155 strain of Mycobacterium smegmatis, a model for Mycobacterium tuberculosis. The findings of the study indicate that exposure to antibiotics did not lead to the development of new adaptive mutations in controlled laboratory environments, challenging the notion that antibiotic resistance arises from drug-induced microevolution. The genomic analysis provides detailed insights into the stability of M. smegmatis following exposure to standard TB treatment antibiotics, and the evidence suggesting that antibiotic pressure does not contribute to the emergence of new adaptive mutations is solid.

eLife Assessment

Yamamoto and Matano provide convincing evidence that a G63E CD8+ T-cell escape mutation in the accessory viral protein Nef facilitates the induction of neutralizing antibody (nAb) responses in rhesus macaques infected with SIVmac239. Functional analyses support that this mutation specifically impairs Nef`s ability to stimulate PI3K/Akt/mTORC2 signalling. This important study suggests that the accessory viral Nef protein impairs B cell function and effective humoral immune responses and is of interest for researchers and physicians interested in HIV/AIDS and vaccine development.

eLife Assessment

This important study presents a significant methodological advance by leveraging previously discarded, unmapped DNA sequence reads to estimate pest infestation loads across plant accessions, and map variation in these apparent pest loads to defense genes. The bioinformatics approach is compelling, and the results should bear broad implications for phenotype-genotype prediction, especially regarding the use of unmapped reads for GWAS.

eLife Assessment

This important study examines the effects of NFKB2 mutations on pituitary gland development through hypothalamic-pituitary organoids. The evidence supporting the main conclusions is solid, although analysis of additional clones to exclude inter-clone variability would strengthen the conclusions. This is a revised study, but insight into the mechanism of action of NFKB2 during pituitary development is incomplete. This work will be of interest to endocrinologists and biologists working on pituitary gland development and disease.

eLife Assessment

This work identifies the molecular function of an orphan human transporter, SLC35G1, providing convincing evidence that this protein is involved in intestinal citrate absorption. This work provides important insight into transporter function and human physiology.

eLife Assessment

This study reports important findings on identifying sequence motifs that predict substrate specificity in a class of lipid synthesis enzymes. It sheds light on a mechanism used by bacteria to modify the lipids in their membrane to develop antibiotic resistance. The evidence is compelling, with a careful application of machine learning methods, validated by mass spectrometry-based lipid analysis experiments. This interdisciplinary study will be of interest to computational biologists and to the community working on lipids and on enzymes involved in lipid synthesis or modification.

eLife Assessment

This important study provides convincing evidence that developing neurons in the neocortex regulate glial cell development. The data demonstrates that the transcription factor FOXG1 negatively regulates gliogenesis by controlling the expression of a member of the FGF ligand family and by suppressing the receptor for this ligand in developing neurons. This study leads to a new understanding of the cascade of events regulating the timing of glial development in the neocortex.