A5057597072- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Axon Guidance and Neuronal Signaling
- Neural dynamics and brain function
- RNA Research and Splicing
- Advanced Fluorescence Microscopy Techniques
- Cellular transport and secretion
- Receptor Mechanisms and Signaling
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Retinal Development and Disorders
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Cellular Mechanics and Interactions
- Anesthesia and Neurotoxicity Research
- Neurobiology and Insect Physiology Research
- Ion channel regulation and function
- Histone Deacetylase Inhibitors Research
- Photochromic and Fluorescence Chemistry
- Neurogenetic and Muscular Disorders Research
- Memory and Neural Mechanisms
- Genetics and Neurodevelopmental Disorders
- Neurogenesis and neuroplasticity mechanisms
- Planarian Biology and Electrostimulation
McGill University Health Centre
2018-2025
Montreal General Hospital
2018-2025
Chinese University of Hong Kong
2025
University of Cambridge
2016-2020
Nascent proteins can be positioned rapidly at precise subcellular locations by local protein synthesis (LPS) to facilitate localized growth responses. Axon arbor architecture, a major determinant of synaptic connectivity, is shaped responses, but it unknown whether LPS influences these responses in vivo. Using high-resolution live imaging, we examined the spatiotemporal dynamics RNA and retinal axons during arborization Endogenous tracking reveals that granules dock sites branch emergence...
Ribosome assembly occurs mainly in the nucleolus, yet recent studies have revealed robust enrichment and translation of mRNAs encoding many ribosomal proteins (RPs) axons, far away from neuronal cell bodies. Here, we report a physical functional interaction between locally synthesized RPs ribosomes axon. We show that axonal RP is regulated through sequence motif, CUIC, forms an RNA-loop structure region immediately upstream initiation codon. Using imaging subcellular proteomics techniques,...
Local translation is rapidly regulated by extrinsic signals during neural wiring, but its control mechanisms remain elusive. Here we show that the extracellular cue Sema3A induces an initial burst in local precisely controls phosphorylation of initiation factor eIF2α via unfolded protein response (UPR) kinase PERK. Strikingly, contrast to canonical UPR signaling, Sema3A-induced bypasses global translational repression and underlies increase through differential activity eIF2B mediated...
During embryonic nervous system assembly, mRNA localization is precisely regulated in growing axons, affording subcellular autonomy by allowing controlled protein expression space and time. Different sets of mRNAs exhibit different patterns across the axon. However, little known about how move axons or these are generated. Here, we couple molecular beacon technology with highly inclined laminated optical sheet microscopy to image single molecules identified endogenous axons. By combining...
Neurotransmission in the brain is unreliable, suggesting that high-frequency spike bursts rather than individual spikes carry neural code. For instance, cortical pyramidal neurons rely on memory formation. Protein synthesis another key factor long-term synaptic plasticity and learning but widely considered unnecessary for transmission. Here, however, we show burst neurotransmission at synapses between neocortical layer 5 cells depends axonal protein linked to presynaptic NMDA receptors mTOR....
Local mRNA translation occurs in growing axons enabling precise control of the proteome response to signals. To measure quantitatively spatiotemporal dynamics protein synthesis growth cones, we further developed a technique for single molecule imaging (SMTI). We report that Netrin-1 triggers burst β-actin at multiple non-repetitive sites, particularly periphery. The is remarkably rapid starting within 20 seconds cue application.
In the textbook view, NMDA receptors (NMDARs) act as coincidence detectors in Hebbian plasticity by fluxing Ca 2+ when simultaneously depolarized and glutamate bound. detection requires that NMDARs be located postsynaptically, but enigmatic presynaptic (preNMDARs) also exist. It is known preNMDARs regulate neurotransmitter release, precisely how remains poorly understood. Emerging evidence suggest can signal non-ionotropically, without need for flux. At synapses between developing visual...
In the textbook view, NMDA receptors (NMDARs) act as coincidence detectors in Hebbian plasticity by fluxing Ca 2+ when simultaneously depolarized and glutamate bound. detection requires that NMDARs be located postsynaptically, but enigmatic presynaptic (preNMDARs) also exist. It is known preNMDARs regulate neurotransmitter release, precisely how remains poorly understood. Emerging evidence suggest can signal non-ionotropically, without need for flux. At synapses between developing visual...
In the textbook view, NMDA receptors (NMDARs) act as coincidence detectors in Hebbian plasticity by fluxing Ca 2+ when simultaneously depolarized and glutamate bound. detection requires that NMDARs be located postsynaptically, but enigmatic presynaptic (preNMDARs) also exist. It is known preNMDARs regulate neurotransmitter release, precisely how remains poorly understood. Emerging evidence suggest can signal non-ionotropically, without need for flux. At synapses between developing visual...
Endocytosis and local protein synthesis (LPS) act coordinately to mediate the chemotropic responses of axons, but link between these two processes is poorly understood. The endosomal sorting complex required for transport (ESCRT) a key regulator cargo in endocytic pathway, here we have investigated role ESCRT-II, critical ESCRT component, Xenopus retinal ganglion cell (RGC) axons. We show that ESCRT-II present RGC axonal growth cones (GCs) where it co-localizes with vesicle GTPases and,...
The transcript encoding translationally controlled tumor protein (Tctp), a molecule correlated with aggressive breast cancers, was identified among the most abundant in genome-wide screens of axons, suggesting that Tctp is important neurons. Here, we tested role retinal axon development Xenopus laevis. We report deficiency results stunted and splayed retinotectal projections fail to innervate optic tectum at normal developmental time due impaired extension. Tctp-deficient axons exhibit...
In the textbook view, N-methyl-d-aspartate (NMDA) receptors are postsynaptically located detectors of coincident activity in Hebbian learning. However, controversial presynaptically NMDA (preNMDARs) have for decades been repeatedly reported literature. These preNMDARs typically implicated regulation short-term and long-term plasticity, but precisely how they signal what their functional roles poorly understood. The across several brain regions different forms plasticity can differ vastly,...
Guidance cues trigger fast responses in axonal growth cones such as directional turning and collapse that require local protein synthesis. An attractive cue-gradient, Netrin-1, triggers de novo synthesis of β-actin localized to the near-side compartment cone promotes F-actin assembly steering. How this precise spatial asymmetry mRNA translation arises across small expanse is poorly understood. Pre-localized mRNAs vicinity activated receptors could be selectively translated and/or new...
Fluorescence anisotropy imaging microscopy (FAIM) measures the depolarization properties of fluorophores to deduce molecular changes in their environment. For successful FAIM, several design principles have be considered and a thorough system-specific calibration protocol is paramount. One important parameter G factor, which describes system-induced errors for different polarization states light. The determination factor discussed detail this article. We present novel measurement strategy,...
SUMMARY Ribosomes are known to be assembled in the nucleolus, yet recent studies have revealed robust enrichment and translation of mRNAs encoding ribosomal proteins (RPs) axons, far away from neuronal cell bodies. Using subcellular proteomics live-imaging, we show that locally synthesized RPs incorporate into axonal ribosomes a nucleolus-independent fashion. We RP is regulated through novel sequence motif, CUIC, forms RNA-loop structure region immediately upstream initiation codon....
ABSTRACT Microcircuit function is determined by patterns of connectivity and short-term plasticity that vary with synapse type. Elucidating microcircuit therefore requires synapse-specific investigation. The state the art for measurements has long been paired recordings. Although powerful, this method slow, leading to a throughput problem. To improve yield, we created optomapping — an approximately 100-fold faster 2-photon optogenetic which validated paired-recording data. Using optomapping,...
Cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent family, is critical for regulating neural development and neuronal survival. Dysregulation Cdk5 associated with abnormal expression cell cycle-related proteins during apoptosis. We have previously found that p35, activator, interacts mSds3, an integral component histone deacetylase complex in vitro, suggesting functional role gene regulation through modulation chromatin integrity. In this study, we further demonstrate...
Abstract Dendritic protein synthesis is a well-known regulator of neurotransmission in the central nervous system. For example, local on-demand dendrites required for hippocampal long-term 1,2 and homeostatic plasticity 3 . Although axonal key neural circuit assembly during early development 4–6 , it unclear if translation mature axons plays functional role mammalian Here we show that regulates pyramidal cell primary visual cortex microcircuits synapse-type-specific manner 7,8 Using paired...