Biology subjects

Jeong, I.

Publications and source records attributed to Jeong, I..

11 recordsLinked to original sources

bioRxiv2025

Brain defence by the extracellular matrix protein Cochlin

The vertebrate brain is protected from infection by tight barriers. However, several barrier structures, including circumventricular organs, can be breached by pathogens. Here, we show that Cochlin, an extracellular matrix-binding protein with anti-bacterial properties, is produced in barrier structures and contributes to immune defence. Transcriptome analysis and in situ hybridisation indicate that cochlin is expressed in the pineal gland, area postrema, choroid plexus and discrete regions of the meninges of zebrafish, mice and humans. The protein is present in the cerebrospinal fluid, and on the surface of ventricle and meninges. Cochlin expression increases in the brain of infected animals and patients, and delivery of recombinant Cochlin reduces bacterial load in zebrafish infected with Mycobacterium marinum. Mutation of cochlin inhibits clearance of bacteria from the brain of zebrafish, and this is reversed by supplying the LCCL domain of Cochlin. Barrier tissues thus contribute to brain defence by secreting Cochlin.

immunology↗

bioRxiv2025

Musicianship and active musical engagement predict facilitation of auditory-motor plasticity: evidence from auditory-motor paired associative stimulation

Background and AimAuditory-motor paired associative stimulation (PAS) probes experience-dependent plasticity in auditory-motor circuits. We tested whether musical experience and musical sophistication modulate PAS-induced facilitation when instrument tones are paired with transcranial magnetic stimulation (TMS) over the left primary motor cortex. MethodSixteen musicians and thirteen non-musicians completed two sessions. Session 1 estimated an individualized inter-stimulus interval (ISI) by testing seven tone-TMS delays (25-300 ms). Session 2 applied PAS at the optimal ISI. Corticospinal excitability was assessed by motor-evoked potentials (MEPs) from right first dorsal interosseus at baseline and post-intervention. Group comparisons and a stepwise multiple regression with Goldsmiths Musical Sophistication Index (Gold-MSI) subscales evaluated predictors of the PAS effect. ResultsA stepwise multiple regression model selected "Group" and "Active Engagement" (Gold-MSI Factor 1) as independent predictors (F (2,26) = 4.59, p = 0.020, adjusted R2 = 0.204), without interaction: musicians exhibited smaller facilitation than non-musicians, and higher Active Engagement predicted greater facilitation across groups. DiscussionThe lack of facilitation in musicians contrasts with somatosensory PAS reports of enhanced plasticity in experts. A modality-specific ceiling effect may contribute, whereby long-term training optimizes auditory-motor transmission, reducing headroom for facilitation. The association with Active Engagement suggests motivational/reward mechanisms--potentially dopaminergic-- gate responsiveness to auditory-motor PAS. ConclusionUnder this protocol, auditory-motor PAS with instrument tones facilitated corticospinal excitability in non-musicians but not in musicians. Individual differences in Active Engagement predicted facilitation, indicating that both group membership and active musical engagement shape susceptibility to auditory-motor associative plasticity.

neuroscience↗

bioRxiv2025

The SAMM50 rs3761472 causes mitochondrial dysfunction and metabolic dysfunction-associated steatotic liver disease

Genome-wide association studies (GWAS) have identified the SAMM50 rs3761472 single nucleotide polymorphism (SNP) as a risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), although its in vivo functions remain unclear. SAMM50 encodes a mitochondrial outer membrane protein critical for maintaining mitochondrial structure. To investigate the biological effects of rs3761472, we generated Samm50-knock-in (KI) mice harboring a D110G substitution using CRISPR/Cas9. This variant impaired mitochondrial integrity by downregulating key regulators of mitochondrial architecture, dynamics, and quality control. This contributed to reduced ATP production and elevated oxidative stress, inflammation, and hepatocyte death. The mutation also induced insulin resistance and glucose intolerance. Samm50-KI mice fed a high-fat diet exhibited pronounced hepatic lipid accumulation and liver injury, highlighting its pathogenic role in MASLD progression. Our findings demonstrate that SAMM50 rs3761472 is a critical driver of mitochondrial dysfunction and MASLD susceptibility, supporting its potential as a therapeutic target and its relevance to precision medicine.

genetics↗

bioRxiv2025

Advection versus diffusion in brain ventricular transport

Cerebrospinal fluid (CSF) is integral to brain function. CSF provides mechanical support for the brain and helps distribute nutrients, neurotransmitters and metabolites throughout the central nervous system. CSF flow is driven by several processes, including the beating of motile cilia located on the walls of the brain ventricles. Despite the physiological importance of CSF, the underlying mechanisms of CSF flow and solute transport in the brain ventricles remain to be comprehensively resolved. This study analyzes and evaluates specifically the role of motile cilia in CSF flow and transport. We developed finite element methods for modeling flow and transport using the geometry of the zebrafish larval brain ventricles, for which we have detailed knowledge of cilia properties and CSF motion. The computational model is validated by in vivo experiments that monitor transport of a photoconvertible protein secreted in the brain ventricles. Our results show that while cilia contribute to advection of large particles, diffusion plays a significant role in the transport of small solutes. We also demonstrate how cilia location and the geometry of the ventricular system impact solute distribution. Altogether, this work presents a computational framework that can be applied to other ventricular systems, together with new concepts of how molecules are transported within the brain and its ventricles.

neuroscience↗

bioRxiv2024

Inhibition mediated by group III mGluRs regulates habenula activity and defensive behaviors

Inhibition contributes to various brain computations from sensory motor transformations to cognitive operations. While most studies on inhibition focus on GABA, the main excitatory neurotransmitter of the brain, glutamate, can also elicit inhibition via metabotropic glutamate receptors (mGluRs). The function of mGluR-mediated inhibition remains largely elusive. Here, we investigated the role of group III mGluR-dependent inhibition in the habenula. This primarily glutamatergic and conserved forebrain region acts as a hub between multiple forebrain inputs and neuromodulatory mid- and hindbrain targets that regulate adaptive behaviors. We showed that both zebrafish and mice habenula express group III mGluRs. We identified that group III mGluRs regulate the membrane potential and calcium activity of zebrafish dorsal habenula. Pharmacological and genetic perturbation of group III mGluRs increased sensory-evoked excitation and reduced selectivity of habenular neurons to different sensory modalities. We also observed that inhibition is the main channel of communication between primarily glutamatergic habenula neurons. Blocking group III mGluRs reduced inhibition within habenula and increased correlations during spontaneous activity. In line with such inhibition within habenula, we identified that multi-sensory information is integrated mainly through competition and suppression across habenular neurons, which in part relies on group III mGluRs. Finally, genetic perturbation of a habenula-specific group III mGluR, mGluR6a, amplified neural responses and defensive behaviors evoked by sensory stimulation and environmental changes. Altogether, our results revealed that mGluR driven inhibition is essential in encoding, integration, and communication of information between Hb neurons, ultimately playing a critical role in regulating defensive and adaptive behaviors.

neuroscience↗

bioRxiv2024

Painting cell-cell interactions by horseradish peroxidase and endogenously generated hydrogen peroxide

Cell-Cell interactions are fundamental in biology for maintaining physiological conditions, with direct contact being the most straightforward mode of interaction. Recent advancements have led to the development of various chemical tools for detecting or identifying these interactions. However, the use of exogenous cues, such as toxic reagents, bulky probes, and light irradiations, can disrupt normal cell physiology. For example, the toxicity of hydrogen peroxide (H2O2) limits the applications of peroxidases in proximity labeling field. In this study, we aimed to address this limitation by demonstrating that membrane-localized Horseradish Peroxidase (HRP-TM) efficiently utilizes endogenously generated extracellular H2O2. By harnessing endogenous H2O2, we observed that HRP-TM-expressing cells can effectively label contacting cells without the need for exogenous H2O2 treatment. Furthermore, we confirmed that HRP-TM labels proximal cells in an interaction-dependent manner. These findings offer a novel approach for studying cell-cell interactions under more physiological conditions, without the confounding effects of exogenous stimuli. Our study contributes to elucidating cell-cell interaction networks in various model organisms, providing valuable insights into the dynamic interplay between cells in their native network.

biochemistry↗

bioRxiv2024

Cilia-mediated cerebrospinal fluid flow modulates neuronal and astroglial activity in the zebrafish larval brain.

The brain uses a specialized system to transport cerebrospinal fluid (CSF). This system consists of interconnected ventricles lined by ependymal cells, which generate a directional flow upon beating of their motile cilia. Motile cilia act jointly with other physiological factors, including active CSF secretion and cardiac pressure gradients, to regulate CSF dynamics. The content and movement of CSF are thought to be important for brain physiology. Yet, the link between cilia-mediated CSF flow and brain function is poorly understood. In this study, we addressed the role of motile cilia-mediated CSF flow on brain development and physiology using zebrafish larvae as a model system. By analyzing mutant animals with paralyzed cilia, we identified that loss of ciliary motility did not alter progenitor proliferation, overall brain morphology, or spontaneous neural activity. Instead, we identified that cilia paralysis led to randomization of brain asymmetry. We also observed altered neuronal responses to photic stimulation, especially in the optic tectum and hindbrain. Since astroglia contact CSF at the ventricular walls and are essential for regulating neuronal activity, we next investigated astroglial activity in motile cilia mutants. Our analyses revealed a striking reduction in astroglial calcium signals both during spontaneous and light-evoked activity. Altogether, our findings highlight a novel role of motile cilia-mediated flow in regulating brain physiology through modulation of neural and astroglial networks.

neuroscience↗

bioRxiv2023

The evolutionary conserved choroid plexus sustains the homeostasis of brain ventricles in zebrafish

The choroid plexus produces cerebrospinal fluid (CSF) by transport of electrolytes and water from the vasculature to the brain ventricles. The choroid plexus plays additional roles in brain development and homeostasis by secreting neurotrophic molecules, and by serving as a CSF-blood barrier and immune interface. Prior studies have identified transporters on the epithelial cells that transport water and ions into the ventricles and tight junctions involved in the CSF-blood barrier. Yet, how the choroid plexus epithelial cells maintain the brain ventricle system and control brain physiology remain unresolved. To provide novel insights into the physiological roles of the choroid plexus, we use juvenile and adult zebrafish as model systems. Upon histological and transcriptomic analyses, we first identified that the zebrafish choroid plexus is highly conserved with the mammalian choroid plexus and that it expresses all transporters necessary for CSF secretion. Using novel genetic lines, we also identified that the choroid plexus secretes proteins into the CSF. Next, we generated a transgenic line allowing us to ablate specifically the epithelial cells in the choroid plexus. Using the ablation system, we identified a reduction of the ventricular sizes, but no alterations of the CSF-blood barrier. Altogether, our findings identified that the zebrafish choroid plexus is evolutionarily conserved and critical for maintaining the size and homeostasis of the brain ventricles. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=163 HEIGHT=200 SRC="FIGDIR/small/565468v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1594039org.highwire.dtl.DTLVardef@877b99org.highwire.dtl.DTLVardef@c3834forg.highwire.dtl.DTLVardef@1e1f787_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe zebrafish choroid plexus has similar anatomical features with the mammalian choroid plexus. C_LIO_LIThe expression of choroid plexus transporters involved in CSF secretion is evolutionarily conserved across vertebrates. C_LIO_LIGeneration of a novel choroid plexus specific driver line shows that the choroid plexus epithelial cells secrete proteins into CSF. C_LIO_LIAblation of the choroid plexus decreases the size of the brain ventricles. C_LI

neuroscience↗

bioRxiv2023

Loss of cilia after neurulation impacts brain development and neuronal activity in larval zebrafish

Cilia are slender, hair-like structures extending from cell surfaces and playing essential roles in diverse physiological processes. Within the nervous system, primary cilia contribute to signaling and sensory perception, while motile cilia facilitate cerebrospinal fluid flow. Here, we investigated the impact of ciliary loss on neural circuit development using a zebrafish line displaying ciliogenesis defects. We found that cilia loss after neurulation affects neurogenesis and brain morphology, and lead to altered gene expression profiles. Using whole brain calcium imaging, we measured reduced light-evoked and spontaneous neuronal activity in all brain regions. By shedding light on the intricate role of cilia in neural circuit formation and function in the zebrafish, our work highlights their evolutionary conserved role in the brain and set the stage for future analysis of ciliopathy models.

neuroscience↗

bioRxiv2023

Foxj1 controls olfactory ciliogenesis and differentiation program of the olfactory sensory neurons

In vertebrates, olfactory receptors localize on multiple cilia elaborated on dendritic knobs of olfactory sensory neurons (OSNs). Although olfactory cilia dysfunction can cause anosmia, how their differentiation is programmed at the transcriptional level has remained largely unexplored. We discovered in zebrafish and mice that Foxj1, a forkhead domain-containing transcription factor linked with motile cilia biogenesis, is expressed in OSNs and required for olfactory epithelium (OE) formation. In keeping with the immotile nature of olfactory cilia, we observed that ciliary motility genes are repressed in zebrafish, mouse, and human OSNs. Strikingly, we also found that besides ciliogenesis, Foxj1 controls the differentiation of the OSNs themselves by regulating their cell type-specific gene expression, such as that of olfactory marker protein (omp) involved in odor-evoked signal transduction. In line with this, response to bile acid, an odor detected by OMP-positive OSNs, was significantly diminished in foxj1 mutant zebrafish. Taken together, our findings establish how the canonical Foxj1-mediated motile ciliogenic transcriptional program has been repurposed for the biogenesis of immotile olfactory cilia and for development of the OSNs.

neuroscience↗

bioRxiv2020

FAM19A5l affects mustard oil-induced peripheral nociception in zebrafish

Family with sequence similarity 19 (chemokine (C-C motif)-like), member A5 (FAM19A5) is a chemokine-like secretory protein recently identified to be involved in the regulation of osteoclast formation, post-injury neointima formation, and depression. Here, we identified FAM19A5l, an orthologous zebrafish gene that originated from a common ancestral FAM19A5 gene. FAM19A5l was expressed in trigeminal and dorsal root ganglion neurons as well as distinct neuronal subsets of the central nervous system of zebrafish. Interestingly, FAM19A5l+ trigeminal neurons were nociceptors that co-localized with TRPA1b and TRPV1, and responded to mustard-oil treatment. Behavioral analysis revealed that the nociceptive response to mustard oil decreased in FAM19A5l-knockout zebrafish larvae. In addition, TRPA1b and NGFa mRNA levels were down- and up-regulated in FAM19A5l-knockout and - overexpressing transgenic zebrafish, respectively. Together, our data suggested that FAM19A5l played a role in nociceptive responses to mustard oil by regulating TRPA1b and NGFa expression in zebrafish.

neuroscience↗