Biology subjects

Zheng, C.

Publications and source records attributed to Zheng, C..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Hydrogel Fiber Endomicroscopy

Multimode fibers enable minimally invasive, high-resolution imaging through ultrathin probes, thereby enhancing diagnostic precision and facilitating real-time monitoring in delicate anatomical regions. In this work, we introduce HYFEN, a hydrogel-based endomicroscopic imaging platform for flexible, biocompatible, and subcellular-scale fluorescence microscopy. HYFEN leverages the unique properties of hydrogel materials, adaptive optics, and pixel-wise image enhancement to address challenges associated with silica-based fibers, including mode scrambling, limited field of view, and mechanical rigidity. The technique achieves precise mode threading, rapid diffraction-limited focusing at kilohertz speeds, and high-fidelity fluorescence signal acquisition with subcellular resolution. Notably, the approach extends fluorescence imaging under enhanced fiber dimensions and bending conditions that are unachievable with conventional modalities. Together, these advances establish HYFEN as a versatile platform for next-generation biointerfacing and minimally invasive imaging across biomedical and clinical settings.

bioengineering↗

bioRxiv2026

Foveated Light-Field Compound Imager

Artificial vision systems hold transformative potential for biomedical imaging, diagnostics, and translational research by emulating and extending the capabilities of biological eyes. However, current techniques often face intrinsic trade-offs between spatial resolution, field of view, and depth perception, particularly in compact, biologically relevant settings. Here, we introduce FOLIC, a foveated light-field compound imaging system, which integrates compound-eye-inspired wide angular coverage and chambered-eye-inspired spatial acuity within a unified multi-aperture concave architecture. FOLIC naturally generates peripheral, blend, and foveated zones from a single capture, enabling seamless, depth-extended, multiscale visualization from wide-field context down to single-cell lateral resolution. We validate FOLIC across diverse fluorescent and non-fluorescent specimens, including cellular phantoms, tissue sections, and small organisms, demonstrating its versatility and scalability for biomedical research and related translational applications. We anticipate FOLIC to offer a biologically informed design blueprint for future artificial vision systems. TeaserA bioinspired system unifies compound and chambered eye principles to achieve wide-field volumetric microscopy.

bioengineering↗

bioRxiv2026

Multi-omics analysis of the potential of MACC1 as a biomarker and therapeutic target for colonic adenocarcinoma

Colonic adenocarcinoma (COAD) is a major cause of cancer-related mortality worldwide. Various tumors are linked to metastasis-associated in colon cancer 1 (MACC1). This study aimed to analyze public datasets to examine MACC1 expression, signaling pathways, copy number variations, and associations with immune cell subsets in COAD employing bioinformatics. MACC1 expression was elevated in COAD, especially in Wnt signaling and chromatin modifier pathways. Analysis of somatic copy number alterations in The Cancer Genome Atlas-COAD dataset revealed a link between MACC1 and DNA damage repair. MACC1 also showed a negative correlation with genes involved in immune cell infiltration in patients with COAD, including cluster of differentiation (CD)8+ T cells, activated dendritic cells, CD8 T cells, and cytotoxic cells. Collectively, these findings suggest MACC1 as a potential prognostic biomarker and therapeutic target for COAD.

cancer biology↗

bioRxiv2026

Gq-pathway activation in hippocampal CA1 astrocytes rescues ischemia-induced memory deficits and synaptic plasticity

More than 30% of stroke survivors develop post-stroke cognitive impairment (PSCI), for which current neuron-centric therapies not only lack cellular specificity but also carry risks of adverse effects such as epilepsy. Here, we explore the therapeutic potential of astrocytes by chemogenetically activating Gq signaling in hippocampal astrocytes, which rescues memory deficits and synaptic plasticity impairments in a mouse model of ischemic stroke. Gq activation restores dendritic complexity, spine density, and long-term potentiation in hippocampal CA1 neurons. Fiber photometry further reveals that astrocytic Ca{superscript 2} signals precede neuronal activity by 600 ms during novel environment exploration, indicating that astrocytes prime memory encoding. In contrast, Gi pathway activation induces pathological neuronal hyperactivity without cognitive improvement. These findings establish that astrocytes regulate post-stroke recovery through pathway-specific calcium signaling and uncover a previously unknown temporal hierarchy in astrocyte-neuron communication during memory processing, offering a new glia-targeted strategy to overcome the limitations of current neuromodulation approaches for PSCI.

neuroscience↗

bioRxiv2026

EnsAgent: a tool-ensemble multiple Agent system for robust annotation in spatial transcriptomics

MotivationAutomated domain annotation in spatially resolved transcriptomics (SRT) remains challenging since it depends on gene expression, morphology, and clinical conventions, which vary across cohorts and platforms. While Large Language Model (LLM)-driven agents show promise, current approaches typically condition semantic reasoning on static, single-method partitions. This reliance makes annotation pipelines fragile to upstream partition errors and prone to hallucinations when molecular evidence is ambiguous. A robust framework integrating ensemble intelligence with iterative, evidence-based reasoning is required to ensure reproducibility and accuracy. ResultsWe introduce EnsAgent, a tool-ensemble multi-agent system designed for robust SRT annotation. Uniquely, EnsAgent decouples structural partitioning from semantic labeling via a Consultation-Review workflow. A Tool-Runner Agent orchestrates a diverse portfolio of clustering algorithms via the Model Context Protocol (MCP), generating a consensus partition optimized by a multimodal Scoring Agent. Subsequently, a Proposer-Critic feedback loop coordinates four specialized experts (Marker, Pathway, Spatiality, and Visual) to formulate annotations with explicit evidence trails and uncertainty estimates. Benchmarking on three SRT datasets demonstrates that EnsAgent effectively neutralizes batch effects and resolves subtle tumor microenvironment niches missed by single-paradigm baselines, delivering state-of-the-art accuracy and interpretability. Availability and ImplementationEnsAgent is available at github.com/keviccz/ensAgent. Contactdongqishi@sztu.edu.cn, kexiao@sztu.edu.cn Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2026

TRPM2 couples cell-autonomous type-I interferon signaling to pigmentation homeostasis

Transient Receptor Potential Melastatin 2 (TRPM2), a Ca{superscript 2}-permeable cation channel, regulates innate and adaptive immunity and has recently been implicated in vitiligo, an autoimmune pigmentary disorder. However, whether TRPM2 exerts cell-autonomous immunoregulatory functions and how such signaling intersects with pigmentation remain unknown. Here, we reveal an unexpected role for TRPM2 as an intrinsic suppressor of pigmentation through type-I interferon (IFN) signaling in melanocytes. Pharmacological inhibition, genetic silencing, and gain-of-function approaches demonstrate that TRPM2 negatively regulates melanogenesis in vitro. Notably, TRPM2-deficient zebrafish and TRPM2-/- mice exhibit enhanced pigmentation in vivo, establishing physiological relevance. Transcriptomic profiling uncovers autonomous activation of the type-I-IFN pathway upon TRPM2 loss, leading to induction of interferon-stimulated gene 15 (ISG15). Mechanistically, ISG15 attenuates global ubiquitination and stabilizes microphthalmia-associated transcription factor (MITF), the master regulator of melanogenesis, thereby promoting pigmentation. Collectively, our findings define a previously unrecognized TRPM2-type-I-IFN-ISG15-MITF signaling axis that functionally integrates cell-autonomous immune surveillance pathways with pigmentary control. Further, it provides a conceptual framework linking type-I interferon signaling to pigmentation homeostasis and pigmentary disorders. Key highlights of the studyO_LITRPM2 negatively regulates pigmentation in vitro (mouse and primary human cells) and in vivo (zebrafish and mice). C_LIO_LIUnbiased RNA-sequencing identifies ISG15 as a positive regulator of melanogenesis downstream of TRPM2 silencing. C_LIO_LITRPM2 knockdown generates a cell autonomous type-I-IFN response in melanocytes that induces ISG15 expression. C_LIO_LIISG15 antagonizes global ubiquitination and regulates stability of MITF, the master regulator of pigmentation. C_LI

cell biology↗

bioRxiv2026

Recessive POPDC1 Truncation Causes Lethal Short-QT Pattern Arrhythmogenic Cardiomyopathy with Multi-Ion Channel Remodeling and Ankyrin-G Scaffold Disruption

AimsBiallelic variants in Popeye domain containing 1 (POPDC1) classically cause limb-girdle muscular dystrophy, but their impact on cardiac system remains unclear. We investigated the functional consequence of a POPDC1 frameshift variant (c.448delT), first identified in a consanguineous family with arrhythmogenic cardiomyopathy (ACM) and sudden death. Methods and resultsComprehensive clinical and genetic evaluation was followed by mechanistic studies in an orthologous Popdc1 knock-in rat model. Functional characterization included biotelemetry and programed electrical stimulation, optical mapping, patch clamp, intracellular Ca2+ imaging, proteomics, and oxidative stress assays. Homozygous mutants (Popdc1fs/fs) exhibited a shortened QTc interval and high incidence of ventricular tachycardia compared to wild-type (Popdc1+/+). Urethane anesthesia provoked second-degree AV block in all 10 Popdc1fs/fs rats but in only 1 of 9 Popdc1+/+ littermates. Optical mapping demonstrated abbreviated action potentials, slowed conduction velocity, and inducible polymorphic VT. Patch clamp confirmed accelerated repolarization, with upregulated transient outward potassium currents (Ito) and L-type calcium currents (ICa, L), but downregulated peak sodium currents (INa). Multi-omics and ultrastructural analyses revealed a post-translational collapse of intercalated disc: POPDC1 loss destabilized Ankyrin-G and its membrane-anchored cargo, Nav1.5, coinciding with enhanced Kv4.3 and Cav1.2 protein levels. These disruptions create a convergence of delayed conduction and shortened refractoriness, forming substrate for malignant re-entry. ConclusionWe defined a recessive short-QT ACM leading to potentially fatal arrhythmias caused by biallelic POPDC1 truncation driving Ankyrin-G disruption, manifesting as a triad: (1) bradycardia/AV block, (2) accelerated repolarization as short-QT pattern/diffuse T-wave flattening or inversion, and (3) progressive cardiomyopathy and sudden death. Whats new?O_LIWe define a novel diagnostic triad for recessive short-QT arrhythmogenic cardiomyopathy (rSQT-ACM) in a loss-of-function POPDC1 truncation: (1) early-onset bradyarrhythmia (sinus bradycardia or AV block); (2) a paradoxical short-QT interval with maladaptive rate response/diffuse T-wave flattening or inversion; and (3) progressive cardiomyopathy accompanied accompanied by with SCD. C_LIO_LIMechanistically, biallelic POPDC1 truncation induces collapse of the POPDC1-AnkG hub, which triggers a unique "opposing remodeling" phenotype (severe INa reduction coupled with paradoxical upregulation of Kv4.3-mediated Ito), and established a unified "slow-conduction, short-wavelength" substrate that underpins malignant re-entry. C_LIO_LIImplications for safety and device therapy: Nav1.5 deficiency indicates that sodium channel blockers may be contraindicated, and early ICD implantation may be preferable to bradycardia pacing. C_LIO_LIMechanism-directed treatments: POPDC1s recessive inheritance and small gene size make it a strong candidate for AAV-mediated gene supplementation aimed at restoring the intercalated disc architecture and ion-channel anchoring. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=76 SRC="FIGDIR/small/710328v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1012d79org.highwire.dtl.DTLVardef@5073dcorg.highwire.dtl.DTLVardef@1e69bc2org.highwire.dtl.DTLVardef@fc15ec_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

genetics↗

bioRxiv2026

Arrestin-3 scaffolds multiple MAP3Ks driving stress-induced JNK3 activation and cell death.

Non-visual arrestin-3 (a.k.a. {beta}-arrestin-2) functions as a scaffold facilitating the activation of c-Jun N-terminal kinases (JNKs), an important pathway regulating cell fate. Here, we demonstrate that arrestin-3 scaffolds not only previously identified ASK1, but facilitates signaling by several MAP3Ks, including ZAK, ZAK{beta}, MEKK1, and TAK1. We identified ZAK (sterile alpha motif and leucine zipper-containing kinase) as the predominant MAP3K mediating arrestin-3-dependent JNK3 signaling and chemotherapy drug-induced cell death in HEK293 cells. We also showed that a 16-residue-long arrestin-3-derived peptide binds ZAK and fulfills the scaffolding function of full-length arrestin-3, sensitizing cells to death induced by chemotherapy drugs. These findings demonstrate that arrestin-3 is a versatile facilitator of stress signaling and suggest that functional peptide mimics can be used therapeutically to facilitate drug-induced death of cancer cells.

cell biology↗

bioRxiv2026

Genomic selection for seed yield enhances flax breeding efficiency

Genomic selection (GS) is a promising strategy to improve breeding efficiency for complex traits such as seed yield by enabling early selection and reducing reliance on extensive field testing. However, practical deployment of GS remains challenging due to limited training populations sizes and reduced predictive ability when models are applied to true breeding germplasm. In this study, we evaluated GS for flax (Linum usitatissimum L.) seed yield under realistic breeding scenarios, with a focus on across-population prediction (APP) and breeding decision support rather than model benchmarking. Using historical germplasm collections and a newly developed breeding-oriented population as training sets, GS performance was assessed across multiple independent test populations representing contemporary breeding lines evaluated in replicated yield trials. APP predictive abilities ranged from r = 0.67 to 0.84 depending on population relatedness when training and test populations were genetically aligned, supporting routine breeding deployment. Training population composition emerged as a key determinant of prediction success, with breeding-oriented populations consistently outperforming broad germplasm collections for predicting true breeding lines. Check-based selection analyses showed that GS reliably reproduced phenotypic advancement decisions while eliminating 61-91% of low-performing lines, resulting in 48-78% reduction in field evaluation costs for a typical cohort of 300 lines. Marker subsampling analyses further indicated that moderate-density genotyping-by-sequencing panels ([~]2,500-3,000 SNPs) are sufficient to achieve stable predictive abilities. Overall, these results demonstrate that GS for seed yield in flax is ready for routine integration into breeding programs, offering a practical pathway to reduce costs, accelerate breeding cycles, and enhance selection efficiency.

genomics↗

bioRxiv2026

Opposing regulatory logics converge on ABA receptors to govern the trade-off between growth and drought acclimation

Plants dynamically balance growth with stress responses through abscisic acid (ABA). How ABA signaling, but how ABA sensitivity is finely tuned is unclear. Here, we uncover a regulatory network of leucine-rich repeat receptor-like kinases (LRR-RLKs) that directly controls ABA receptors stability. We identify GASSHO1 (GSO1) as a core component that phosphorylates the PYL2 and PYL4 receptors, targeting them for degradation and thus serving as a brake on ABA signaling. Under drought stress, ABA accumulates and suppresses expression of GSO1-activating CIF peptides, releasing this brake to increase PYLs and sensitivity. This mechanism opposes our previously identified CEPR2 pathway, where drought-induced CEP peptides inhibit the kinase to stabilize PYLs. The integration of these two antagonistic modules within an LRR-RLK network enables precise, dynamic control of ABA perception. This work reveals a molecular framework explaining how plants calibrate the critical balance between growth and drought acclimation.

molecular biology↗

bioRxiv2026

Lipid monounsaturation confers cold tolerance and improves tissue viability during hypothermic storage

The rapid loss of tissue viability during hypothermic storage frequently results in organ failure and high discard rates in transplantation. In contrast, ectothermic animals can tolerate prolonged exposure to low temperatures in their natural environments. Elucidating the mechanisms underlying this cold tolerance may therefore inform improved strategies for tissue preservation. Here, we investigate proteomic and metabolomic responses to cold exposure in the livers of two frog species from distinct habitats: the cold-sensitive African clawed frog (Xenopus laevis) and the cold-tolerant Northeastern Asian brown frog (Rana dybowskii). Cold exposure induced lipid mobilization in X. laevis, whereas it promoted phospholipid mono-unsaturation in R. dybowskii. Notably, treatment with monounsaturated fatty acids (MUFAs) or overexpression of stearoyl-CoA desaturase (SCD) reduced cell death during cold storage. Moreover, MUFA infusion significantly improved cell viability in mouse liver tissue under hypothermic conditions. Together, these findings suggest that lipid mono-unsaturation, an adaptive feature of cold-tolerant frogs, can be leveraged to enhance tissue preservation during cold storage.

biochemistry↗

bioRxiv2026

MultiGS: A comprehensive and user-friendly genomic prediction platform Integrating statistical, machine learning, and deep learning models for breeders

Genomic selection (GS) is a core strategy in modern breeding programs, yet the rapid expansion of statistical, machine-learning (ML), and deep-learning (DL) models has made systematic evaluation and practical deployment increasingly challenging. To address these issues, we developed MultiGS, a unified and user-friendly framework that integrates linear, ML, DL, hybrid, and ensemble GS models within a standardized and computationally efficient workflow. MultiGS is implemented through two complementary pipelines: MultiGS-R, a Java/R pipeline implementing 12 statistical and ML models, and MultiGS-P, a Python pipeline integrating 17 models including five linear models, three ML approaches, and nine recently developed DL architectures implemented within the framework. We benchmarked MultiGS using wheat, maize, and flax datasets representing contrasting prediction scenarios. Wheat and maize were evaluated using random training-test splits within the same population, reflecting suitable conditions for assessing model capacity and scalability. Under these scenarios, several DL, hybrid, and ensemble models achieved prediction accuracies comparable to RR-BLUP and consistently exceeded those of GBLUP. In contrast, the flax dataset represented a true across-population prediction scenario with limited training set size and strong population structure. In this challenging context, classical linear models provided stable baselines, while a subset of DL architectures--particularly graph-based models and BLUP-integrated hybrids--demonstrated comparatively improved generalization across populations. Comparisons with previously published DL tools showed that MultiGS models achieved comparable or improved prediction accuracies while requiring lower computational costs, enabling routine retraining and large-scale evaluation. Overall, MultiGS informs, scenario-specific model selection and provides a practical platform for deploying genomic prediction under realistic breeding conditions. The software is freely available on GitHub (https://github.com/AAFC-ORDC-Crop-Bioinfomatics/MultiGS).

bioinformatics↗

bioRxiv2025

Silicon Micropillar-Enhanced CRISPR Biosensor for Rapid and Sensitive Detection of Drug-Resistant Bacteria

1The growing threat of antibiotic-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), underscores the urgent need for rapid, sensitive, and field-deployable diagnostic technologies. Here, we present a silicon micropillar-enhanced CRISPR biosensor that integrates high-aspect-ratio microstructures with a one-pot RPA/CRISPR-Cas12a assay for ultrasensitive and specific detection of MRSA. Micropillar arrays with fixed diameters and varying heights (100 {micro}m, 300 {micro}m, and 500 {micro}m) were fabricated via deep reactive ion etching and functionalized for surface probe immobilization. Suboptimal crRNA design was employed to modify Cas12a activation kinetics, enabling declined trans-cleavage and enhanced end-point signal accumulation. The 500 {micro}m micropillar configuration demonstrated a tenfold improvement in sensitivity compared to the 100 {micro}m array, with a limit of detection reaching 103 CFU mL-1. The platform also showed high specificity against non-target bacterial strains. These findings highlight the potential of combining microstructured chips with one-pot CRISPR diagnostics to advance next-generation point-of-care tools for infectious disease monitoring. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=184 SRC="FIGDIR/small/694528v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@5f5f7corg.highwire.dtl.DTLVardef@175cb35org.highwire.dtl.DTLVardef@7043e5org.highwire.dtl.DTLVardef@79aa15_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Preserved Neural Dynamics across Arm- and Brain-controlled Movements

The neural activity for motor control is complex and dynamic; it has been found to dramatically transit from planning to executing movements. As brain-machine interfaces (BMIs) can directly connect the brain and the external world by yielding comparable motor outcomes with artificial apparatus, a central question is whether the BMI-controlled movements share neural dynamics or underlying mechanism with natural movements. To enable a systematic comparison, we developed a feedforward BMI framework with distinct planning and executing epochs that enables ballistic cursor control to intercept moving targets. This BMI allowed monkeys to voluntarily initiate neural states which controlled the direction and timing to launch a ballistic movement, like skeet shooting. Based on this, we found similar neural representations and computational structures across arm- and brain-controlled conditions. Notably, in addition to resembling the rotational structure in natural reaching, the neural population dynamics during open-loop BMI also shared preserved manifolds with those during reaching arm movements. These findings suggest a fundamental principle, and reveal a set of basic computational motifs for the neural control of movement in an abstract hierarchy in the absence of constraints from actuators. This study thus has the potential to reshape the consideration of how BMIs assist paralyzed patients in interacting with dynamic environments, and to promote next-generation BMI systems.

neuroscience↗

bioRxiv2025

sept-1/zina-1 is an Ancient Toxin-Antidote System in Caenorhabditis elegans

The toxin-antidote (TA) systems, consisting of two tightly linked genes acting as a postzygotic distorter, are found in several eukaryotic organisms, including three androdioecious Caenorhabditis species. However, the evolutionary history of such TA systems remains poorly understood. We report an ancient C. elegans TA system identified in the highly divergent Hawaiian strain XZ1516. The maternal toxin SEPT-1 induces a rod-like larval arrest phenotype in progeny that do not carry the antidote ZINA-1, which has ten zinc finger motifs. Interestingly, zina-1 is pseudogenized in most non-Hawaiian strains, while sept-1 evolves from a toxic to a non-toxic form through sequence divergence. Phylogenetic studies found that sept-1/zina-1 is the most ancestral TA system among the three known ones, and its loss preceded the rise of sup-35/pha-1. These two maternal TAs do not coexist in the same strain but have overlaps with the paternal TA peel-1/zeel-1, which is the latest one to propagate.

evolutionary biology↗

bioRxiv2025

LEM-3/ANKLE1 nuclease prevents the formation of syncytium between postmitotic sister cells and safeguards neuronal differentiation

In animal development, cells exit the cell cycle after a final division to differentiate into specialized types. However, the impact of failed cytokinesis on the fate specification of postmitotic cells, especially neurons, remain poorly understood. We analysed 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 canals, creating binucleate syncytia between touch receptor neurons and sisters, 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.

developmental biology↗

bioRxiv2025

Genotype imputation and error estimation in connected multiparental populations

Multiparental populations have been produced for quantitative trait loci (QTL) mapping in many crops, where next-generation sequencing has become a cost-effective tool for genotyping. Previously, we have developed a hidden Markov framework denoted by MagicImpute_mma for genotype imputation in a multiparental population, which was implemented in Mathematica. However, its computational time increases quickly with the number of parents. In this work, we extend MagicImpute_mma into MagicImpute for increasing computational efficiency and robustness to various types of errors. Particularly, it has the following novel features: (1) allowing for multiple multiparental populations that may be connected by sharing parents, (2) allowing for many missing parents that are not available for sequencing, (3) accounting for allelic bias and overdispersion in next generation sequencing data, (4) inferring marker-specific error rates and filtering for markers with low error rates, and (5) being implemented in the high performance Julia language. Besides extensive simulation studies, we evaluate MagicImpute by three real datasets: the rice F2 population with sequence depth being low, the apple F1 population with parents being outbred, and the sorghum multi-parent advanced generation inter-cross (MAGIC) population with 10 male sterile lines (out of 29 parents) being missing. The results have shown that MagicImpute is accurate for genotype imputation in connected bi- or multiparental populations with various types of sequence errors and it opens up new opportunities for QTL mapping after imputing many missing parents.

bioinformatics↗

bioRxiv2025

Synaptic and neural pathway redundancy enables the robustness of a sensory-motor reflex and promotes predation escape in C. elegans

As a basic unit of the nervous system, the sensory-motor reflex circuit is fast and robust. However, it is not entirely clear how this robustness is achieved, given that various genetic perturbations can disrupt the function of the sensory neurons. By mapping the molecular basis of neuronal connections in the touch response circuit of Caenorhabditis elegans, we found prevalent genetic redundancy at neural pathway, synaptic, and molecular levels, which ensures that sensory signals can be relayed to command interneurons that control motor output. We also discovered developmental remodeling of the anterior circuit, which leads to the pruning of larval synapses, establishment of a second pathway that activates additional interneurons, and lateralization of the circuit. Finally, we found that the synapses that appeared to be functionally redundant in a simple touch assay contribute to the extent of reversal response in an additive manner, which may help the organism escape from predators.

neuroscience↗