A5058650953- Cancer Genomics and Diagnostics
- Neurogenesis and neuroplasticity mechanisms
- DNA Repair Mechanisms
- Developmental Biology and Gene Regulation
- Lung Cancer Treatments and Mutations
- Cancer Treatment and Pharmacology
- Epigenetics and DNA Methylation
- Axon Guidance and Neuronal Signaling
- RNA Research and Splicing
- MicroRNA in disease regulation
- Pluripotent Stem Cells Research
- Hereditary Neurological Disorders
- CRISPR and Genetic Engineering
- Nerve injury and regeneration
- Genetics and Neurodevelopmental Disorders
- Single-cell and spatial transcriptomics
- Congenital heart defects research
- Glioma Diagnosis and Treatment
- Wnt/β-catenin signaling in development and cancer
- Cellular transport and secretion
- Hedgehog Signaling Pathway Studies
- Anesthesia and Neurotoxicity Research
- Immune cells in cancer
- 3D Printing in Biomedical Research
- Neuroscience and Neuropharmacology Research
University of Basel
2015-2024
University Hospital of Basel
1994-2021
Biogipuzkoa Health Research Institute
2015
Max Planck Institute of Immunobiology and Epigenetics
2003-2013
University of Sheffield
2010-2012
Max Planck Society
2005-2011
University of Freiburg
2010
École Polytechnique Fédérale de Lausanne
1995-2002
ETH Zurich
2000-2001
Novartis (Switzerland)
1991
The generation of new neurons from neural stem cells in the adult hippocampal dentate gyrus contributes to learning and mood regulation. To sustain neurogenesis throughout life, maintenance cell pool has be tightly controlled. We found that Notch/RBPJκ-signaling pathway is highly active mouse hippocampus. Conditional inactivation RBPJκ vivo resulted increased neuronal differentiation hippocampus at an early time point depletion Sox2-positive suppression a later point. Moreover,...
Abstract Emerging evidence suggests that new cells, including neurons, can be generated within the adult hypothalamus, suggesting existence of a local neural stem/progenitor cell niche. Here, we identify α-tanycytes as key components hypothalamic niche in mouse. Long-term lineage tracing vivo using GLAST::CreER T2 conditional driver indicates are self-renewing cells constitutively give rise to tanycytes, astrocytes and sparse numbers neurons. In vitro studies demonstrate α-tanycytes, but not...
The mechanisms that guide progenitor cell fate and differentiation in the vertebrate central nervous system (CNS) are poorly understood. Gain-of-function experiments suggest Notch signaling is involved early stages of mammalian neurogenesis. On basis expression Notch1 by putative cells CNS, we have addressed directly role development brain. Using conditional gene ablation, show loss results premature onset neurogenesis neuroepithelial midbrain-hindbrain region neural tube. Notch1-deficient...
The adult mammalian forebrain contains neural stem/progenitor cells (NSCs) that generate neurons throughout life. As in other somatic stem cell systems, NSCs are proposed to be predominantly quiescent and proliferate only sporadically produce more committed progeny. However, quiescence has recently been shown not an essential criterion for cells. It is known whether show differences molecular dependence based on their proliferation state. subventricular zone (SVZ) of the mouse brain a...
Abstract Discrimination of neural stem cells from other progenitors in the developing mammalian brain has been hampered by lack specific markers. Identifying progenitor pools and signalling pathways that guide neurogenesis are central to understanding complex mechanisms govern development nervous system. Notch plays a pivotal role system maintaining multipotent regulating their fate. In order identify putative situ , we generated transgenic mice express Green Fluorescent Protein (GFP) report...
Neural stem cells (NSCs) in the ventricular domain of subventricular zone (V-SVZ) rodents produce neurons throughout life while those humans become largely inactive or may be lost during infancy. Most adult NSCs are quiescent, express glial markers, and depend on Notch signaling for their self-renewal generation neurons. Using genetic markers lineage tracing, we identified subpopulations V-SVZ (type 1, 2, 3) indicating a striking heterogeneity including activated, brain lipid binding protein...
Neurogenesis continues in the ventricular-subventricular zone (V-SVZ) of adult forebrain from quiescent neural stem cells (NSCs). V-SVZ NSCs are a reservoir for new olfactory bulb (OB) neurons that migrate through rostral migratory stream (RMS). To generate neurons, need to activate and enter cell cycle. The mechanisms underlying NSC transition quiescence activity poorly understood. We show Notch2, but not Notch1, signaling conveys by repressing cell-cycle-related genes neurogenesis. Loss...
In the adult brain, subsets of astrocytic cells residing in well-defined neurogenic niches constitutively generate neurons throughout life. Brain lesions can stimulate neurogenesis otherwise non-neurogenic regions, but whether local these conditions is unresolved. Here, through genetic and viral lineage tracing mice, we demonstrate that striatal astrocytes become following an acute excitotoxic lesion. Similar to germinal niches, activated parenchymal progenitors express nestin formation...
Abstract Multigene delivery and subsequent cellular expression is emerging as a key technology required in diverse research fields including, synthetic structural biology, reprogramming functional pharmaceutical screening. Current viral systems such retro- adenoviruses suffer from limited DNA cargo capacity, thus impeding unrestricted multigene expression. We developed MultiPrime, modular, non-cytotoxic, non-integrating, baculovirus-based vector system expediting highly efficient transient...
Neural stem cells (NSCs) in the adult mouse hippocampal dentate gyrus (DG) are mostly quiescent, and only a few cell cycle at any point time. DG NSCs become increasingly dormant with age enter mitosis less frequently, which impinges on neurogenesis. How NSC inactivity is maintained largely unknown. Here, we found that Id4 downstream target of Notch2 signaling maintains quiescence by blocking cell-cycle entry. expression sufficient to promote knockdown rescues Notch2-induced inhibition...
Abstract Neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to brain repair during CNS disease. The microenvironment within SVZ stem cell niche controls NSPC fate. However, extracellular factors that trigger astrogliogenesis over neurogenesis disease are unclear. Here, we show blood-derived fibrinogen is enriched in following distant cortical injury mice. Fibrinogen inhibited neuronal differentiation and hippocampal NSPCs while promoting...
Abstract Mutations in glucocerebrosidase cause the lysosomal storage disorder Gaucher’s disease and are most common risk factor for Parkinson’s disease. Therapies to restore enzyme’s function brain hold great promise treating neurological implications. Thus, we developed blood-brain barrier penetrant therapeutic molecules by fusing transferrin receptor-binding moieties β-glucocerebrosidase (referred as GCase-BS). We demonstrate that these fusion proteins show significantly increased uptake...
Peripheral myelin protein 22 (PMP22) is expressed in many tissues but mainly by Schwann cells as a component of compact the peripheral nervous system (PNS). Mutations affecting PMP22 are associated with hereditary motor and sensory neuropathies. Although these phenotypes restricted to PNS, thought play dual role formation cell proliferation.We describe cloning characterization epithelial membrane protein-1 (EMP-1), putative four-transmembrane 160 amino acids 40% acid identity PMP22. EMP-1...
Notch1 and beta1-integrins are cell surface receptors involved in the recognition of niche that surrounds stem cells through cell-cell cell-extracellular matrix interactions, respectively. is also control fate choices developing central nervous system (Lewis, J. (1998) Semin. Cell Dev. Biol. 9, 583-589). Here we report Notch co-expressed these proteins cooperate with epidermal growth factor receptor neural progenitors. We describe data suggests may affect signaling 1) physical interaction...