A5047692405- Axon Guidance and Neuronal Signaling
- Amyotrophic Lateral Sclerosis Research
- Neurogenesis and neuroplasticity mechanisms
- Zebrafish Biomedical Research Applications
- Microtubule and mitosis dynamics
- Genetic Neurodegenerative Diseases
- Angiogenesis and VEGF in Cancer
- Genetic and Kidney Cyst Diseases
- Mitochondrial Function and Pathology
- Cholinesterase and Neurodegenerative Diseases
- Hedgehog Signaling Pathway Studies
- Prion Diseases and Protein Misfolding
- Cellular Mechanics and Interactions
- Molecular spectroscopy and chirality
- Elasticity and Material Modeling
- Retinal Development and Disorders
- Developmental Biology and Gene Regulation
- Biochemical Acid Research Studies
- ATP Synthase and ATPases Research
- Congenital heart defects research
- Parkinson's Disease Mechanisms and Treatments
- Cellular transport and secretion
- Photosynthetic Processes and Mechanisms
- Growth Hormone and Insulin-like Growth Factors
- Hippo pathway signaling and YAP/TAZ
Utrecht University
2019-2024
University Medical Center Utrecht
2019-2024
Institut de la Vision
2012-2017
Inserm
2012-2017
Sorbonne Université
2014-2017
Centre National de la Recherche Scientifique
2014-2017
University College London
2012
Medizinische Hochschule Hannover
2012
Heidelberg University
2004-2008
Clearing techniques have been developed to transparentize mouse brains, thereby preserving 3D structure, but their complexity has limited use. Here, we show that immunolabeling of axonal tracts followed by optical clearing with solvents (3DISCO) and light-sheet microscopy reveals brain connectivity in embryos postnatal brains. We the Robo3 receptor is selectively expressed medial habenula axons forming fasciculus retroflexus (FR) analyzed development this commissural tract mutants Slit/Robo...
Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease and lacks effective disease-modifying treatments. This study utilizes comprehensive multiomic approach to investigate the early sex-specific molecular mechanisms underlying ALS. By analyzing prefrontal cortex of 51 patients with sporadic ALS 50 control subjects, alongside four transgenic mouse models (C9orf72-, SOD1-, TDP-43-, FUS-ALS), we have uncovered significant alterations associated disease. Here, show that...
Intermediate-length repeat expansions in ATAXIN-2 (ATXN2) are the strongest genetic risk factor for amyotrophic lateral sclerosis (ALS). At molecular level, ATXN2 intermediate enhance TDP-43 toxicity and pathology. However, whether this triggers ALS pathogenesis at cellular functional level remains unknown. Here, we combine patient-derived mouse models to dissect effects of an background. iPSC-derived motor neurons from ATXN2-ALS patients show altered stress granules, neurite damage abnormal...
Rationale: The Slit–Roundabout (Robo) signaling pathway has pleiotropic functions during Drosophila heart development. However, its role in mammalian development is largely unknown. Objective: To analyze the of Slit–Robo formation pericardium and systemic venous return murine heart. Methods Results: Expression genes encoding Robo1 Robo2 receptors their ligands Slit2 Slit3 was found or around Analysis embryos lacking revealed partial absence pericardium, whereas Robo1/2 double mutants...
During cell migration or differentiation, surface receptors are simultaneously exposed to different ligands. However, it is often unclear how these extracellular signals integrated. Neogenin (NEO1) acts as an attractive guidance receptor when the Netrin-1 (NET1) ligand binds, but mediates repulsion via repulsive molecule (RGM) Here, we show that signal integration occurs through formation of a ternary NEO1-NET1-RGM complex, which triggers reciprocal silencing downstream signaling. Our...
Gonadotropin-releasing hormone (GnRH) neurons are born in the nasal placode and migrate along olfactory vomeronasal axons to reach forebrain settle hypothalamus, where they control reproduction. The molecular cues that guide their migration have not been fully identified, but thought either cell movement directly or patterning of axonal substrates. Using genetically altered mouse models we show GnRH is modulated by Slit2 Robo3, members axon guidance Slit ligand Robo receptor families. Mice...
We investigated the role of cell adhesion molecule NrCAM for axonal growth and pathfinding in developing retina. Analysis distribution pattern chick embryo retina sections flat-mounts shows its presence during extension retinal ganglion (RGC) axons; is selectively present on RGC axons absent from soma. Single cultures show an enrichment distal axon cone. When offered as a substrate addition to Laminin, promotes formation cone protrusions. In stripe assays, mimicking NrCAM-displaying optic...
ABSTRACT During the development of central nervous system (CNS), only motor axons project into peripheral nerves. Little is known about cellular and molecular mechanisms that control a boundary at CNS surface prevent neuron emigration from neural tube. It has previously been shown subset spinal cord commissural abnormally invades sensory nerves in Ntn1 hypomorphic embryos Dcc knockouts. However, whether netrin 1 also plays similar role brain unknown. In hindbrain, precerebellar neurons...
Abstract Progressive loss of motor neurons is the hallmark neurodegenerative disease amyotrophic lateral sclerosis (ALS), but underlying mechanisms remain incompletely understood. In this study, we investigate effects C21ORF2 mutations, a gene recently linked to ALS, and find that primary cilia are dysfunctional. Human patient-derived mutant have reduced ciliary frequency length. We report located at basal body cilium, mutations associated with ALS alter localization. Furthermore, show...
During development, precerebellar neurons migrate tangentially from the dorsal hindbrain to floor plate. Their axons cross it but their cell bodies stop ventral migration upon reaching midline. It has previously been shown that Slit chemorepellents and receptors, Robo1 Robo2, might control of in a repulsive manner. Here, we have used conditional knockout strategy mice test this hypothesis. We show targeted inactivation expression Robo2 receptors does not perturb they still at The selective...
DM-GRASP, cell adhesion molecule of the immunoglobulin superfamily, has been shown to promote growth and navigation axons. We here demonstrate that clustering DM-GRASP in plasma membrane induces its rapid internalization via dynamin- clathrin-dependent endocytosis, which is controlled by phosphatidylinositol 3-kinase mitogen-activated protein kinase ERK. The activates ERK; intensity duration ERK activation do not depend on clathrin-mediated DM-GRASP. Moreover, preference retinal ganglion...
SUMMARY Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease that affects 1 in 400 people. Almost 40 genes have been associated with ALS, currently explaining about 15% of the ALS risk. These tend to cluster certain pathways such as protein quality control, RNA metabolism and axonal function. Despite these advances, adequate treatments for patients are still missing. In this study, we investigate role newly discovered gene, C21orf2 , pathology. We show...
Abstract Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and lacks effective disease-modifying treatments. Here, we performed a multiomic analysis of prefrontal cortex 51 patients with sporadic ALS 50 control subjects, as well four transgenic mouse models C9orf72-, SOD1-, TDP-43-, FUS-ALS to characterize early sex-specific mechanisms in ALS. Integrated analyses transcriptomes, (phospho)proteomes, miRNAomes revealed more pronounced changes males. We identified...
Abstract Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, which still lacks effective disease-modifying therapies. Similar to other neurodegenerative disorders, such as Alzheimer and Parkinson ALS pathology presumed propagate over time, originating from cortex spreading cortical regions. Exploring early disease stages crucial understand causative molecular changes underlying pathology. For this, we sampled human postmortem prefrontal (PFC) tissue Brodmann area 6,...