Biology subjects

Nguyen, K. C. Q.

Publications and source records attributed to Nguyen, K. C. Q..

13 recordsLinked to original sources

bioRxiv2026

Lysosome-related organelle genes are required for mitochondrial transformations during bacterial infections in Caenorhabditis elegans.

Detecting and responding to pathogenic bacteria is an essential function of eukaryotic cells. As bacteria-derived organelles, mitochondria carry lipids, proteins, and other molecules such as iron which are required for bacterial growth, and thus are subject to pathogenic bacterial attack. In fact, mitochondrial morphology and function are often altered during early bacterial infection. However, the mechanism by which bacterial pathogen attack triggers mitochondrial responses is unknown. Here, we demonstrate that infection by the pathogenic bacterium Staphylococcus aureus or Pseudomonas aeruginosa or hypoxia leads to remodeling of the mitochondrial network in the host Caenorhabditis elegans. Our analysis discovers that lysosome-related organelle (LRO) genes are required for this remodeling and indicates that LROs also precipitate downstream infection-response gene expression.

immunology↗

bioRxiv2026

Comparative connectomics reveals stage-specific gap junction rewiring that reshapes avoidance behavior

Environmental stress can remodel neural circuits, yet how such rewiring generates behavioral adaptation remains poorly understood. The dauer stage of Caenorhabditis elegans provides a unique model to address this question. Here, we investigated how dauer-specific circuit remodeling alters nociceptive behavior. We found that dauers exhibit markedly shorter avoidance durations than adults. Comparative connectomics revealed substantial expansion of gap junctions within the dauer nociceptive circuit. Calcium imaging further showed that dauer neurons exhibit faster and more transient activity dynamics throughout the circuit. Introducing synthetic dauer-specific gap junctions into adults was sufficient to recapitulate dauer-like neuronal activity patterns and significantly shorten avoidance duration. Despite extensive circuit rewiring, however, avoidance initiation remained preserved across developmental stages. Together, our findings demonstrate that the dauer connectome is selectively rewired through gap junction remodeling to tune behavioral persistence while robustly preserving behavioral initiation, revealing how developmental circuit reorganization balances flexibility and stability for survival under stress.

neuroscience↗

bioRxiv2026

The extracellular matrix gene mec-9 regulates C. elegans sensory cilia

Cilia are critical sensory organelles that project from the cell surface into the tissue environment, where they are surrounded by extracellular matrix (ECM). Abnormal ECM and fibrosis are two hallmarks of ciliopathies, yet the relationship between cilia and ECM is not well understood. Using the sense organs of C. elegans as a model, we found that a neomorphic mutation in the ECM gene mec-9 impacts sensory cilia function, ciliary protein localization, microtubule ultrastructure, and shedding of ciliary extracellular vesicles (EVs). We show that mec-9 is not expressed in EV releasing neurons, but rather by companion neurons in the sense organs, and may act cell non-autonomously. Our studies reveal pleiotropic roles for mec-9 in the C. elegans ciliated nervous system and provide an in vivo model to study the relationship between cilia and ECM.

cell biology↗

bioRxiv2026

Apical spectrin organizes cortical actin filament bundles to pattern C. elegans cuticle ridges

The apical extracellular matrix can form elaborate three-dimensional structures on animal surfaces. To better understand the mechanisms that pattern and shape these structures, we focus on development of collagen-rich cuticle ridges (alae) in adult C. elegans. Previous studies suggested that longitudinal actin filament bundles (AFBs) in the lateral seam epidermis specify alae position through a mechanism that involves post-secretory matrix delamination. Here we identify additional components of this highly organized cortical actin network and show that loss of the apical {beta}H-spectrin SMA-1 specifically disrupts organization of the two AFBs that would normally flank the site where the middle alae ridge forms. Correspondingly, sma-1 loss, or mutation of its actin binding domains, also disrupts formation of the middle alae ridge. Ultrastructurally, sma-1 mutants have expanded regions of matrix delamination that can explain middle ridge loss. Together, these data highlight the importance of apical spectrin for organizing a patterned actin network within epithelia and show that, via its effects on actin organization, spectrin can also change the extracellular matrix and its patterns on animal surfaces.

developmental biology↗

bioRxiv2024

Structural diversity of mitochondria in the neuromuscular system across development

As an animal matures, its neural circuit undergoes alterations, yet the developmental changes in intracellular organelles to facilitate these changes is less understood. Using 3D electron microscopy and deep learning, we developed semi-automated methods for reconstructing mitochondria in C. elegans and collected mitochondria reconstructions from normal reproductive stages and dauer, enabling comparative study on mitochondria structure within the neuromuscular system. We found that various mitochondria structural properties in neurons correlate with synaptic connections and these properties are preserved across development in different neural circuits. To test the necessity of these universal mitochondria properties, we examined the behavior in drp-1 mutants with impaired mitochondria fission and discovered that it caused behavioral deficits. Moreover, we observed that dauer neurons display distinctive mitochondrial features, and mitochondria in dauer muscles exhibit unique reticulum-like structure. We propose that this specialized mitochondria structure may serve as an adaptive mechanism to support stage-specific behavioral and physiological needs.

neuroscience↗

bioRxiv2023

Cell-specific alpha-tubulin TBA-6 and pan-ciliary IFT cargo RAB-28 generate a non-canonical transition zone

The transition zone (TZ) regulates cilia composition and function. Canonical TZs with 9 doublet microtubules (MTs) are common but non-canonical TZs that vary from 9 MT symmetry also occur and arise through unknown mechanisms. Cilia on the quadrant inner labial type 2 (IL2Q) neurons of C. elegans have a specialized non-canonical TZ with fewer than 9 doublet MTs. We previously showed that non-canonical TZs in IL2Q cilia arise via MT loss and reorganization of canonical TZs. Here, we identify structural events and mechanisms that generate non-canonical TZs. Cell-specific -tubulin TBA-6 and pan-ciliary IFT cargo RAB-28 regulate IL2QTZ MT loss without affecting ciliary assembly. Our results reveal a role for the tubulin code in generating non-canonical TZs and contribute towards understanding ciliary functional specialization. Author summaryCiliary microtubules are exquisitely diverse in arrangements and composition. Studies on how ciliary ultrastructural diversity is generated are essential to our understanding of cilia function in diverse healthy and pathological contexts. Despite its clinical relevance, the ultrastructural diversity of the transition zone and its microtubules remains understudied. Here, we uncover mechanisms contributing to generating ultrastructural diversity in the transition zone and in cilia. A subset of sensory cilia in C. elegans contain a non-canonical transition zone with 7 and fewer doublet microtubules. We previously showed that this distinct transition zone is generated through microtubule loss in a canonical transition zone with 9 doublet microtubules, a process that occurs asynchronously during animal development. Here, we identify roles for the tubulin code and for an IFT cargo in generating a distinct transition zone. Sculpting of the distinct transition zone occurs in fully assembled cilia and transition zones and is independent of general ciliogenesis mechanisms. Our results demonstrate how specialized transition zones can be generated from canonical transition zones and provide insight into mechanisms of ciliary ultrastructural diversity and post-ciliogenesis restructuring. Such mechanisms hold the key to understanding ciliary function and to restoration of function in ciliopathies with ciliary ultrastructural defects.

cell biology↗

bioRxiv2023

Mind of a dauer: Comparative connectomics reveals developmental plasticity

A fundamental question in neurodevelopmental biology is how flexibly the nervous system changes during development. To address this, we reconstructed the complete connectome of dauer, an alternative developmental stage of nematodes with distinct behavioral characteristics, by volumetric reconstruction and automated synapse detection using deep learning. With the basic architecture of the nervous system preserved, structural changes in neurons, large or small, were closely associated with connectivity changes, which in turn evoked dauer-specific behaviors such as nictation. Graph theoretical analyses revealed significant dauer-specific rewiring of sensory neuron connectivity and increased clustering within motor neurons in the dauer connectome. We suggest that the nervous system in the nematode, probably animals in general, has evolved to respond to harsh environments by reversibly developing a quantitatively and qualitatively differentiated connectome.

neuroscience↗

bioRxiv2021

A transient apical extracellular matrix relays cytoskeletal patterns to shape permanent acellular ridges on the surface of adult C. elegans

Apical extracellular matrices can form protruding structures such as denticles, ridges, scales, or teeth on the surfaces of epithelia. The mechanisms that shape these structures remain poorly understood. Here, we show how the actin cytoskeleton and a provisional matrix work together to sculpt acellular longitudinal alae ridges in the cuticle of adult C. elegans. Transient actomyosin-dependent constriction of the underlying lateral epidermis accompanies deposition of the provisional matrix at the earliest stages of alae formation. Actin is required to pattern the provisional matrix into longitudinal bands that are initially offset from the pattern of longitudinal actin filaments. These bands appear ultrastructurally as alternating regions of adhesion and separation within laminated provisional matrix layers. The provisional matrix is required to establish these demarcated zones of adhesion and separation, which ultimately give rise to alae ridges and their intervening valleys, respectively. Provisional matrix proteins shape the alae ridges and valleys but are not present within the final structure. We propose a morphogenetic mechanism wherein cortical actin patterns are relayed mechanically to the laminated provisional matrix to set up distinct zones of matrix layer separation and accretion that shape a permanent and acellular matrix structure.

developmental biology↗

bioRxiv2021

Kinesin-3 mediated delivery of presynaptic neurexin stabilizes growing dendritic spines and postsynaptic components in vivo

The functional properties of neural circuits are defined by the patterns of synaptic connections between their partnering neurons, but the mechanisms that stabilize circuit connectivity are poorly understood. We systemically examined this question at synapses onto newly characterized dendritic spines of C. elegans GABAergic motor neurons. We show that the presynaptic adhesion protein, neurexin/NRX-1, is required for stabilization of postsynaptic structure. We find that early postsynaptic developmental events proceed without a strict requirement for synaptic activity and are not disrupted by deletion of neurexin/nrx-1. However, in the absence of presynaptic NRX-1, dendritic spines and receptor clusters become destabilized and collapse prior to adulthood. We demonstrate that kinesin-3/UNC-104 delivers NRX-1 to presynaptic terminals and show that ongoing delivery is required for postsynaptic maintenance in mature animals. By defining the dynamics and temporal order of synapse formation events in vivo, we describe a mechanism for stabilizing mature circuit connectivity through neurexin-based adhesion.

neuroscience↗

bioRxiv2020

F-box protein MEC-15 promotes microtubule stability and neurite growth by antagonizing the HSP90 chaperone network in Caenorhabditis elegans

Molecular chaperones often work collaboratively with the ubiquitination-proteasome system (UPS) to facilitate the degradation of misfolded proteins, which typically safeguards cellular differentiation and protects cells from stress. In this study, however, we report that the Hsp70/Hsp90 chaperone machinery and an F-box protein, MEC-15, have opposing effects on neuronal differentiation and that the chaperones negatively regulate neuronal morphogenesis and functions. Using the touch receptor neurons (TRNs) of Caenorhabditis elegans, we find that mec-15(-) mutants display defects in microtubule formation, neurite growth, synaptic development, and neuronal functions, and these defects can be rescued by the loss of Hsp70/Hsp90 chaperones and cochaperones. MEC-15 likely functions in a SCF complex to degrade DLK-1, which is an Hsp90 client protein stabilized by the chaperones. The abundance of DLK-1, and likely other Hsp90 substrates, is fine-tuned by the antagonism between MEC-15 and chaperones; this antagonism regulates TRN development as well as synaptic functions of GABAergic motor neurons. Therefore, a balance between UPS and chaperones tightly controls neuronal differentiation. Summary statementMolecular chaperones are known to protect cells from stress. However, in this study the authors showed that the Hsp90 chaperone negatively regulates neuronal differentiation when the ubiquitination-proteasome system is compromised.

developmental biology↗

bioRxiv2019

A ciliary BBSome-ARL-6-PDE6D pathway trafficks RAB-28, a negative regulator of extracellular vesicle biogenesis

Cilia both receive and send information, the latter in the form of extracellular vesicles (EVs). EVs are nano-communication devices that cells shed to influence cell, tissue, and organism behavior. Mechanisms driving ciliary EV biogenesis and environment release are almost entirely unknown. Here, we show that the ciliary G-protein RAB28, associated with human autosomal recessive cone-rod dystrophy, negatively regulates EV levels in the sensory organs of Caenorhabditis elegans. We also find that sequential targeting of lipidated RAB28 to periciliary and ciliary membranes is highly dependent on the BBSome and PDE6D, respectively, and that BBSome loss causes excessive and ectopic EV production. Our data indicate that RAB28 and the BBSome are key in vivo regulators of EV production at the periciliary membrane. Our findings also suggest that EVs control sensory organ homeostasis by mediating communication between ciliated neurons and glia, and that defects in ciliary EV biogenesis may contribute to human ciliopathies.

cell biology↗

bioRxiv2018

Cell type-specific structural plasticity of the ciliary transition zone in C. elegans

Background informationThe current consensus on cilia development posits that the ciliary transition zone (TZ) is formed via extension of nine centrosomal microtubules. In this model, TZ structure remains unchanged in microtubule number throughout the cilium life cycle. This model does not however explain structural variations of TZ structure seen in nature, and could also lend itself to the misinterpretation that deviations from nine-doublet microtubule ultrastructure represent an abnormal phenotype. Thus, a better understanding of events that occur at the TZ in vivo during metazoan development is required.\n\nResultsTo address this issue, we characterized ultrastructure of two types of sensory cilia in developing Caenorhabditis elegans. We discovered that, in cephalic male (CEM) and inner labial quadrant (IL2Q) sensory neurons, ciliary TZs are structurally plastic and remodel from one structure to another during animal larval development. The number of microtubules doublets forming the TZ can be increased or decreased over time, depending on cilia type. Both cases result in structural TZ intermediates different from TZ in adult cilia. In CEM cilia, axonemal extension and maturation occurs concurrently with TZ structural maturation.\n\nConclusions and SignificanceOur work extends the current model to include the structural plasticity of metazoan transition zone, which can be structurally delayed, maintained or remodeled in cell type-specific manner.

cell biology↗

bioRxiv2018

Extracellular matrix regulates morphogenesis and function of ciliated sensory organs in Caenorhabditis elegans

Cilia and extracellular vesicles (EVs) are signaling organelles that play important roles in human health and disease. In C. elegans and mammals, the Autosomal Dominant Polycystic Kidney Disease (ADPKD) gene products polycystin-1 and polycystin-2 localize to both cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation. Hence, the nematode offers an excellent system in which to address central questions regarding the biology of cilia, EVs, and the polycystins. We discovered an unexpected role of the mec-1, mec-5, and mec-9 genes encoding extracellular matrix (ECM) components. We determined that these ECM encoding genes regulate polycystin localization and function, ciliary EV release, cilia length, dendritic morphology, and neuron-glia interactions. Abnormal ECM and fibrosis are observed in ciliopathies such as ADPKD, nephronophthisis, and Bardet-Biedl Syndrome. Our studies reveal multifaceted roles for ECM proteins in the ciliated nervous system of the worm and provide a powerful new in vivo model to study the relationship between ECM, the polycystins, and ciliopathies.

cell biology↗