A5088222971- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Lung Cancer Treatments and Mutations
- Cancer Treatment and Pharmacology
- Developmental Biology and Gene Regulation
- Epigenetics and DNA Methylation
- Neuroinflammation and Neurodegeneration Mechanisms
- Axon Guidance and Neuronal Signaling
- Olfactory and Sensory Function Studies
- Anesthesia and Neurotoxicity Research
- MicroRNA in disease regulation
- CRISPR and Genetic Engineering
- Immune cells in cancer
- Neuroendocrine regulation and behavior
- Glioma Diagnosis and Treatment
- Neuroscience and Neuropharmacology Research
- Hedgehog Signaling Pathway Studies
- Single-cell and spatial transcriptomics
- Nerve injury and regeneration
- Pluripotent Stem Cells Research
- Cell Adhesion Molecules Research
- CAR-T cell therapy research
- Cellular Mechanics and Interactions
- Air Quality Monitoring and Forecasting
University of Basel
2013-2024
University Hospital of Basel
2021
University Hospital Schleswig-Holstein
2018
University of Lübeck
2018
Max Planck Institute of Immunobiology and Epigenetics
2009-2013
Max Planck Society
2009-2011
Accademia Albertina delle Belle Arti
2001-2009
University of Turin
2001-2007
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 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...
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...
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...
The subventricular zone (SVZ) is regarded as an embryonic germinal layer persisting at the end of cerebral cortex neurogenesis and capable generating neuronal precursors throughout life. two distinct compartments adult rodent forebrain SVZ, astrocytic glial tubes chains migrating cells, are not distinguishable in early postnatal counterpart. In this study we analyzed SVZ mice rats around birth different stages, describing molecular morphological changes which lead to typical structural...
The transcription factor cAMP response element-binding protein (CREB) is involved in multiple aspects of neuronal development and plasticity. Here, we demonstrate that CREB regulates specific phases adult neurogenesis the subventricular zone/olfactory bulb (SVZ/OB) system. Combining immunohistochemistry with bromodeoxyuridine treatments, cell tracer injections, transplants, quantitative analyses, show although expressed by SVZ neuroblasts throughout neurogenic process, its phosphorylation...
Adult neurogenesis is tightly regulated through the interaction of neural stem/progenitor cells (NSCs) with their niche. Neurotransmitters, including GABA activation GABAA receptor ion channels, are important niche signals. We show that adult mouse hippocampal NSCs and progeny express metabotropic GABAB receptors. Pharmacological inhibition receptors stimulated NSC proliferation genetic deletion GABAB1 subunits increased differentiation neuroblasts in vivo. Cell-specific conditional supports...
Immune surveillance is critical to prevent tumorigenesis. Gliomas evade immune attack, but the underlying mechanisms remain poorly understood. We show that glioma cells can sustain growth independent of system constraint by reducing Notch signaling. Loss activity in a mouse model impairs MHC-I and cytokine expression curtails recruitment anti-tumor cell populations favor immunosuppressive tumor-associated microglia/macrophages (TAMs). Depletion T simulates inhibition facilitates tumor...
In the olfactory bulb of adult rodents, local interneurons are constantly replaced by immature precursors derived from subventricular zone. Whether any sensory process specifically relies on this cell renewal remains largely unclear. By using well-known model mating-induced imprinting, we demonstrate that memory formation critically depends presence newborn granule neurons in accessory bulb. Accordingly, show that, female mice, exposure to male pheromones increases number new cells surviving...
Generation of gain-of-function transgenic mice by targeting the Rosa26 locus has been established as an alternative to classical produced pronuclear microinjection. However, transgenes endogenous promoter results in moderate ubiquitous expression and is not suitable for high levels. Therefore, we now generated a modified (modRosa26) that combines efficient targeted transgenesis using recombinase-mediated cassette exchange (RMCE) Flipase (Flp-RMCE) or Cre recombinase (Cre-RMCE) with transgene...
Abstract Newborn neurons generated by proliferative progenitors in the adult subventricular zone (SVZ) integrate into olfactory bulb circuitry of mammals. Survival these newly‐formed cells is regulated input. The presence new accessory (AOB) has already been demonstrated some mammalian species, albeit their neurochemical profile and functional integration AOB circuits are still to be investigated. To unravel whether mouse represents a site constitutive neurogenesis this process can modulated...
The subventricular zone (SVZ) of the lateral ventricles is major neurogenic region in adult mammalian brain, harbouring neural stem cells within defined niches. identity these and factors regulating their fate are poorly understood. We have genetically mapped a population Nestin-expressing during postnatal development to study potential vivo. Taking advantage recombination characteristics nestin::CreER(T2) allele, we followed subpopulation traced largely unrecombined niche. Perinatal...
Adult hippocampal neurogenesis is a remarkable form of brain plasticity through which new neurons are generated throughout life. Despite its important roles in cognition and emotion modulation various preclinical disease models, the functional importance adult human health has not been revealed because lack tools for monitoring vivo. Therefore, we performed an unbiased proteomics screen to identify novel proteins expressed during neuronal differentiation using neural stem cell model,...
Abstract Blood-borne metastasis of breast cancer involves a series tightly regulated sequential steps, including the growth primary tumor lesion, intravasation circulating cells (CTC), and adaptation in various distant metastatic sites. The genes orchestrating each these steps are poorly understood physiologically relevant contexts, owing to rarity experimental models that faithfully recapitulate biology, kinetics, tropism human cancer. Here, we conducted an vivo loss-of-function CRISPR...