A5082190768- Neurogenesis and neuroplasticity mechanisms
- MicroRNA in disease regulation
- Zebrafish Biomedical Research Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Nerve injury and regeneration
- RNA Research and Splicing
- Neuroscience, Education and Cognitive Function
- Neuroscience and Neuropharmacology Research
- Electrochemical sensors and biosensors
- Axon Guidance and Neuronal Signaling
- Cellular transport and secretion
- CRISPR and Genetic Engineering
- Lipid Membrane Structure and Behavior
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Analytical Chemistry and Sensors
- Creativity in Education and Neuroscience
- Microtubule and mitosis dynamics
- Photoreceptor and optogenetics research
- Cellular Mechanics and Interactions
- Grit, Self-Efficacy, and Motivation
- Personal Information Management and User Behavior
- RNA regulation and disease
- Neurobiology and Insect Physiology Research
- Nerve Injury and Rehabilitation
University of Edinburgh
2016-2025
Multiple Sclerosis Society
2013-2024
Royal Society of Edinburgh
2024
Discovery Centre
2020
Multiple Sclerosis Society of Canada
2017
Mott MacDonald (United Kingdom)
2013-2016
The majority of axons in the central nervous system (CNS) are eventually myelinated by oligodendrocytes, but whether timing and extent myelination vivo reflect intrinsic properties or regulated axons, remains undetermined. Here, we use zebrafish to study CNS at single-cell resolution vivo. We show that large caliber Mauthner axon is first be (shortly before smaller caliber) presence supernumerary can profoundly affect single oligodendrocytes. Oligodendrocytes typically myelinate just one...
Highlights•Live imaging of myelin sheath dynamics along single axons over time in zebrafish•Vesicular release from reticulospinal required for normal myelination•Vesicular CoPA not myelination•Evidence neuronal subtype diversity activity-regulated myelinationSummaryRegulation myelination by oligodendrocytes the CNS has important consequences higher-order nervous system function (e.g., [1–4]), and there is growing consensus that activity regulates [5–9]) through local axon-oligodendrocyte...
Myelin is required for rapid nerve signaling and emerging as a key driver of CNS plasticity disease. How myelin built remodeled remains fundamental question neurobiology. Central to myelination the ability oligodendrocytes add vast amounts new cell membrane, expanding their surface areas by many thousand-fold. However, how membrane build or remodel not fully understood. Here, we show that addition requires exocytosis mediated vesicular SNARE proteins VAMP2/3. Genetic inactivation VAMP2/3 in...
Myelination of axons by oligodendrocytes enables fast saltatory conduction. Oligodendrocytes are responsive to neuronal activity, which has been shown induce changes myelin sheaths, potentially optimize conduction and neural circuit function. However, the cellular bases activity-regulated myelination in vivo unclear, partly due difficulty analyzing individual myelinated over time. Activity-regulated occurs specific subtypes can be mediated synaptic vesicle fusion, but several questions...
Myelin, the insulating sheath that surrounds neuronal axons, is produced by oligodendrocytes in central nervous system (CNS). This evolutionary innovation, which first appears jawed vertebrates, enabled rapid transmission of nerve impulses, more complex brains, and greater morphological diversity. Here, we report RNA-level expression RNLTR12-int, a retrotransposon retroviral origin, essential for myelination. We show RNLTR12-int-encoded RNA binds to transcription factor SOX10 regulate myelin...
The correct targeting of myelin is essential for nervous system formation and function. Oligodendrocytes in the CNS myelinate some axons, but not others, do structures including cell bodies dendrites [1Lubetzki C. Demerens Anglade P. Villarroya H. Frankfurter A. Lee V.M. Zalc B. Even culture, oligodendrocytes solely axons.Proc. Natl. Acad. Sci. USA. 1993; 90: 6820-6824Crossref PubMed Scopus (111) Google Scholar]. Recent studies indicate that extrinsic signals, such as neuronal activity...
SUMMARY Optical recording of intricate molecular dynamics is becoming an indispensable technique for biological studies, accelerated by the development new or improved biosensors and microscopy technology. This creates major computational challenges to extract quantify biologically meaningful spatiotemporal patterns embedded within complex rich data sources, many which cannot be captured with existing methods. Here, we introduce Activity Quantification Analysis (AQuA2), a fast, accurate,...
Selection of the correct targets for myelination and regulation myelin sheath growth are essential central nervous system (CNS) formation function. Through a genetic screen in zebrafish complementary analyses mice, we find that loss oligodendrocyte Neurofascin leads to mistargeting cell bodies, without affecting targeting axons. In addition, reduces CNS by impairing growth. Time-lapse imaging reveals distinct myelinating processes individual oligodendrocytes can engage target selection at...
Optical recording of intricate molecular dynamics is becoming an indispensable technique for biological studies, accelerated by the development new or improved biosensors and microscopy technology. This creates major computational challenges to extract quantify biologically meaningful spatiotemporal patterns embedded within complex rich data sources, many which cannot be captured with existing methods. Here, we introduce activity quantification analysis (AQuA2), a fast, accurate, versatile...
Oligodendrocytes form myelin around axons of the central nervous system, enabling saltatory conduction. Recent work has established that can regulate certain aspects oligodendrocyte development and myelination, yet remarkably oligodendrocytes in culture retain ability to differentiate absence elaborate sheaths synthetic axon-like substrates. It remains unclear extent which life-course requires presence of, or signals derived from vivo. In particular, it is whether specific fated for...
In this study, we describe the adaptation of split Gal4 system for zebrafish. The Gal4-UAS is widely used expression genes-of-interest by crossing driver lines expressing transcription factor (under control promoter interest) with reporter where upstream activating sequence (UAS) repeats (recognized Gal4) drive genes-of-interest. Split system, hemi-drivers separately encode DNA-binding domain (DBD) and activation (AD) Gal4. When encoded under two different promoters, only those cells in...
Through a genetic screen in zebrafish, we identified mutant with disruption to myelin both the CNS and PNS caused by mutation previously uncharacterized gene, slc12a2b, predicted encode Na+, K+, Cl- (NKCC) cotransporter, NKCC1b. slc12a2b/NKCC1b mutants exhibited severe progressive pathology PNS, characterized dysmyelination swelling of periaxonal space at axon-myelin interface. Cell-type-specific loss either neurons or myelinating Schwann cells recapitulated these pathologies. Given that...
The spacing of nodes Ranvier crucially affects conduction properties along myelinated axons. It is assumed that node position primarily driven by growing myelin sheaths. Here, we reveal an additional mechanism positioning the axon. Through longitudinal live imaging formation dynamics in zebrafish central nervous system, show stable clusters cell adhesion molecule neurofascin a can accumulate at specific sites axons prior to myelination. While some these are pushed into future extending...
Targeted knock-in of fluorescent reporters enables powerful gene and protein analyses in a physiological context. However, precise integration long sequences remains challenging vivo. Here, we demonstrate cloning-free reporter into zebrafish genes, using PCR-generated templates for homology-directed repair with short homology arms (PCR tagging). Our novel lines vesicle-associated membrane (vamp) homologues reveal subcellular complexity this family. approach fast efficient the genome (in...
To study activity-regulated myelination, we imaged synaptic vesicle fusion along single axons in living zebrafish, and found, surprisingly, that axonal is driven by myelination. This myelin-induced was enriched the unmyelinated domains into which newly-formed sheaths grew, promoted neuronal activity, turn accelerated sheath growth. Our results indicate activity consolidates growth already selected for
Abstract Myelinating Schwann cells of the peripheral nervous system (PNS) express numerous ion channels and transporters, have capacity to respond neuronal activity. However, it remains unknown how response activity affects nerve formation, health or function in vivo. Through a genetic screen zebrafish, we identified mutant, ue58 , with severe disruption morphology myelin along nerves associated oedema. Molecular analyses indicated that this phenotype was caused by loss previously...