A5020195440- Wnt/β-catenin signaling in development and cancer
- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Axon Guidance and Neuronal Signaling
- Alzheimer's disease research and treatments
- Microtubule and mitosis dynamics
- Neurogenesis and neuroplasticity mechanisms
- Cancer-related gene regulation
- Developmental Biology and Gene Regulation
- Nuclear Receptors and Signaling
- Nerve injury and regeneration
- Cellular transport and secretion
- Ion channel regulation and function
- Photoreceptor and optogenetics research
- Cellular Mechanics and Interactions
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurobiology and Insect Physiology Research
- Mitochondrial Function and Pathology
- Iron Metabolism and Disorders
- Hedgehog Signaling Pathway Studies
- Bacterial Genetics and Biotechnology
- Vibrio bacteria research studies
- Computational Drug Discovery Methods
- Plant Micronutrient Interactions and Effects
- Legume Nitrogen Fixing Symbiosis
University College London
2015-2024
Universidad Santo Tomás
2024
Universidad Nacional de Asunción
2022-2024
Cardiff University
2023
UK Dementia Research Institute
2023
MRC Laboratory for Molecular Cell Biology
2020-2022
Imperial College London
2000-2022
Consejo Nacional de Ciencia y Tecnología
2022
Clínica Alemana
2016
Universidad del Desarrollo
2016
ABSTRACT WNT-7a induces axonal spreading and branching in developing cerebellar granule neurons. This effect is mediated through the inhibition of GSK-3β, a serine/threonine kinase component WNT pathway. Lithium, an inhibitor mimics cells. Here we examined further GSK-3β on cytoskeletal re-organisation. Lithium increases growth cone area perimeter. associated with absence or reduction stable microtubules spread areas. loss phosphorylated form MAP-1B, microtubule protein involved outgrowth....
Proper dialogue between presynaptic neurons and their targets is essential for correct synaptic assembly function. At central synapses, Wnt proteins function as retrograde signals to regulate axon remodeling the accumulation of proteins. Loss Wnt7a leads defects in localization markers morphology axons. We show that loss Dishevelled-1 (Dvl1) mimics enhances phenotype cerebellum. Although active zones appear normal, electrophysiological recordings cerebellar slices from Wnt7a/Dvl1 double...
Dishevelled (DVL) is associated with axonal microtubules and regulates microtubule stability through the inhibition of serine/threonine kinase, glycogen synthase kinase 3β (GSK-3β). In canonical WNT pathway, negative regulator Axin forms a complex β-catenin GSK-3β, resulting in degradation. Inhibition GSK-3β by DVL increases TCF transcriptional activation. Here, we show that associates unexpectedly stabilizes DVL. turn, inhibiting transcription- β-catenin–independent pathway. More...
In the mammalian cochlea, stereociliary bundles located on mechanosensory hair cells within sensory epithelium are unidirectionally oriented. Development of this planar polarity is necessary for normal hearing as only sensitive to vibrations in a single plane; however, mechanisms governing their orientation unknown. We report that Wnt signaling regulates development unidirectional bundle orientation. vitro application Wnt7a protein or inhibitors signaling, secreted Frizzled-related 1...
The balance between excitatory and inhibitory synapses is crucial for normal brain function. Wnt proteins stimulate synapse formation by increasing synaptic assembly. However, it unclear whether signaling differentially regulates the of synapses. Here, we demonstrate that Wnt7a preferentially stimulates In hippocampal neurons, increases number synapses, whereas are unaffected. or postsynaptic expression Dishevelled-1 (Dvl1), a core component, frequency amplitude miniature currents (mEPSCs),...
Extensive evidence supports a central role for amyloid-β (Aβ) in the pathogenesis of Alzheimer's disease (AD). Synaptic loss mediated by Aβ early stages might contribute to cognitive impairments. However, little is known about mechanism which induces synapses. The expression Wnt antagonist Dickkopf-1 (Dkk1) increased brains AD patients and transgenic mouse models, suggesting that dysfunction signaling could pathology. Here we report acute exposure oligomers Dkk1 together with synaptic sites....
Axon guidance and target-derived signals control axonal behavior by regulating the cytoskeleton through poorly defined mechanisms. In particular, how these signaling molecules regulate growth directionality of microtubules is not well understood. Here we examine effect Wnts on cone remodeling, a process that precedes synapse formation. Time-lapse recordings reveal Wnt3a rapidly inhibits translocation while inducing enlargement. These changes in are associated with organization microtubules....
Synapse degeneration occurs early in neurodegenerative diseases and correlates strongly with cognitive decline Alzheimer's disease (AD). The molecular mechanisms that trigger synapse vulnerability those promote regeneration after substantial synaptic failure remain poorly understood. Increasing evidence suggests a link between deficiency Wnt signaling AD. secreted antagonist Dickkopf-1 (Dkk1), which is elevated AD, contributes to amyloid-β-mediated failure. However, the impact of Dkk1 at...
Wnt proteins play a crucial role in several aspects of neuronal circuit formation. Wnts can signal through different receptors including Frizzled, Ryk and Ror2. In the hippocampus, Wnt7a stimulates formation synapses; however, its receptor remains poorly characterized. Here, we demonstrate that Frizzled-5 (Fz5) is expressed during peak synaptogenesis mouse hippocampus. Fz5 present synaptosomes colocalizes with pre- postsynaptic markers vGlut1 PSD-95. Expression early stages increases number...
Significance The accurate quantification of the amounts small oligomeric assemblies formed by amyloid β (Aβ) peptide represents a major challenge in Alzheimer’s field. There is therefore great interest development methods to specifically detect these oligomers distinguishing them from larger aggregates. availability will enable effective diagnostic and therapeutic interventions for this other diseases related protein misfolding aggregation. We describe here single-domain antibody able...