Neural stem cells

…are generated during development by neural stem and progenitor cells. Epigenetic mechanisms play a pivotal role in orchestrating the behaviour of stem cells during development. We are interested in the mechanisms that regulate gene expression in neural stem cells, which have implications for our understanding of neocortex development an

…the correct production of distinct neural and glial cell types. This process is partially regulated by the modification of chromatin structure by epigenetic complexes, including the Polycomb group (PcG) family of co-repressors. Genetic screening has identified several PcG mutations that are causally associated with a range of congenital brain disorders, yet the specific regulatory roles of Polycomb complexes during normal neurodevelopment is still unclear. Here, we inve

…and diminished the proliferation of neural stem cells. Additionally, our findings i

Radial glia (RG) are the principal neural stem cells of the embryonic brain, giving rise to neural cell types and serving as mechanical scaffold for neuron migration. Ln2PMMA is an RG biomimetic substrate, of poly methyl methacrylate with 2μm linear topography, that reproduced the surface properties and mechanical anisotropy of the embryonic RG niche. Mechanical signals from ln2PMMA induce cultured astrocytes to dedifferentiate into functional RG. However, the mechanotransducive components underlying this process are largely unknown. We used mouse cortical glial cultures grown on control and l

During embryonic and postnatal development of the dentate gyrus (DG), neural stem cells (NSCs) proliferate, migrate and generate mature granule neurons. Unlike other brain regions, NSCs remain in the adult DG, mostly in a state of deep quiescence, with the ability to re-enter cell cycle and generate new neurons throughout life. The transitions back and forward from a proliferative state to a temporal shallow quiescence or primed state ensure the maintenance of stem cell population. However, it is unclear when and how adult NSCs acquire quiescence sub-states during development. Recently, we hav

…organ size, proliferation, and stem cell signaling in multiple tissue systems. However, their roles in nervous system development and neuronal differentiation have been understudied. Here, we set out to characterize YAP/TAZ expression changes and function in human neurogenesis in a cell lineage-specific and/or developmental stage-specific manner. To this end, YAP and TAZ knockouts were created in human embryonic stem cells using CRISP

…about the effect of galectin-3 on neural cells. Our work aims to determine the effect of galecitn-3 on neurogenesis and on glial clearance of Aβ. Neurospheres generated from primary murine neural stem cells were treated with galectin-3 or the galectin-3 inhibitor TD139. Proliferation, as determined by neurosphere size after 5 days, was decreased in neurospheres treated with galectin-3. Differentiation, as quantified by proportion o

Adult neurogenesis, the differentiation of new neurons from neural stem cells (NSCs), occurs primarily within the subventricular zone (SVZ) and the hippocampal dentate gyrus (DG). Caffeine, the most widely used psychostimulant, is a potent non-selective adenosine receptor antagonist. Though the adenosinergic system has been shown to regulate adult brain plasticity, caffeine impact on postnatal neurogenesis and synaptogenesis remains elusive. Thus, the main goal of this work was to dissect caffeine effects on the differentiation and maturation of postnatal NSCs into neurons.Our results indicate

FOXG1 is a transcription factor essential for brain development. Mutations in FOXG1 perturb forebrain development and are commonly associated with neurodevelopmental conditions such as autism and epilepsy. These conditions often also co-occur and preliminary studies have suggested a convergent aetiology. Thus studying the biological functions of FOXG1 and providing mechanistic insight into its functions can better reveal the molecular and cellular aetiology of these conditions. This will help us accelerate biomarker discovery and therapeutic strategies for epilepsy in individuals with or witho

Prader-Willi Syndrome (PWS) is a neurodevelopmental disorder caused by the loss of the expression of the paternally expressed genes contained at PWS locus, located at chromosome 15 in humans. The most common molecular cause of the syndrome is a deletion of some of the genes located in this cluster, and specifically, a critical region (PWScr) has been postulated as the minimal deletion capable of giving rise to a PWS phenotype. This region contains several tandem-repeated copies of snoRNA-coding gene SNORD116 and the non-coding gene IPW. In adult mammals, new neurons are produced along the whol

…Since neural stem cells are key players in the expansion of neural cell pools throughout development, we hypothesized that a group of ASD-risk gen

Neurogenesis is the process where neural stem cells (NSCs) develop into functional neurons. It comprises proliferation, differentiation, migration, axonal and dendritic targeting, and synaptic integration. Meropenem is a broad-spectrum carbapenem that treats various infections. It can penetrate most body fluids and tissues, cross the blood–brain barrier, and obtain a concentration within the cerebrospinal fluid close to that of blood plasma. However, no research has established a link between meropenem and neurotoxic effects on the brain and the subsequent behavioral activity. This project aim

In the adult brain, subsets of astrocytes act as neural stem cells in two specialized niches, the sub-ventricular zone and hippocampal dentate gyrus, where they produce olfactory bulb interneurons and dentate gyrus granule cells throughout life. In specific conditions the genesis of new neurons can occur also outside these niches in the adult brain parenchyma. This ectopic neurogenesis is prominent in the striatum where it occurs in both physiologic, in adult rabbits and adolescent guinea pigs, or pathologic conditions, such as mouse models of both progressive and acute neuronal degeneration.

…It is created by re-aggregating neural stem cells from multiple single-cell donor organoids in a manner that allows each donor to produce all cell lineages of the cerebral cortex, even when using pluripotent stem cell lines with notable growth biases. We leveraged Chimeroids to investigate inter-indiv

Periventricular heterotopia (PH) is a cortical malformation characterized by misplaced neurons adjacent to the lateral ventricles, commonly associated with epilepsy. It is genetically diverse, and its underlying mechanisms are not fully understood. While recent research suggests that neuronal differentiation can also be affected, it has traditionally been considered a neuronal migration disorder, supported by the identification of mutations in neuronal-enriched cytoskeletal genes. Furthermore, it is still unclear why only some neurons are affected in this condition, while the majority of other

The meninges are a protective and nutritious tissue that surrounds the central nervous system (CNS) and supports the brain. Recent data, including from our team, have revealed that the meninges contain a myriad of immune cells, such as meningeal macrophages (MM). Interestingly, the meninges penetrate the brain parenchyma and contact sub-structures such as the hippocampus, which is one of the main neurogenic niches. This strategic position of the meninges and thus MM raised the hypothesis that these cells could play a role in hippocampal neonatal neurogenesis. To address this question, we used

…Additionally, neural progenitor cells might be adversely affected by chemotherapeutic drugs, extinguishing any possibility of nervous tissue regeneration (Dietrich et al., 2006). This emphasizes the importance of precisely targeting cancer cells while preserving healthy brain cells. This work aims at addressing this challenge through the development of poly

…which new neurons arise from dentate neural stem cells (NSCs). Current research of our group suggests that NSCs are affected in their fate decisions by AD. We observed an increased proliferation of NSCs in the pre-plaque phase which is followed by a strong decline in the number of NSCs and adult neurogenesis. Factors modulating NSC proliferation du

Neural stem cells (NSCs) in the adult mouse brain contribute to lifelong brain plasticity. NSCs in the adult ventricular-subventricular zone (V-SVZ) are heterogeneous and, depending on their location in the niche, give rise to different types of olfactory bulb interneurons. We have recently showed that pregnancy activates specific stem cell subpopulations residing in regionally-distinct domains of the niche, with different temporal dynamics. The recruitment of ‘pregnancy-associated’ NSCs is transient, and results in a temporally-controlled generation of different subtypes of olfactory bulb int

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the formation of amyloid-β (Aβ) plaques and Tau neurofibrillary tangles, leading to neuronal loss, inflammation, reduced neurogenesis, and cognitive impairment. Currently, there is no effective cure for AD, highlighting the urgent need for novel therapeutic strategies. Growth hormone-releasing hormone (GHRH) and its agonistic analog MR-409 exhibit several peripheral functions, including neuroprotection and protection against skeletal muscle atrophy. However, the role of GHRH in AD remains to be elucidated. Our in vitro f

…(CB) has been proposed as a niche of neural stem cells because, in vitro, cells from this area are able to form neurospheres, proliferate and differentiate. Here, we explore the potential of CB cells to differentiate and replace degenerated retinal ganglion cells (RGCs) in vivo. CB cells isolated from adult retinas and intravitreally injected into the retina of mice that had been previously depleted of RGCs by optic nerve axotomy, integrate into the ganglion cell layer and express neuronal markers. A different type of

In the adult mammalian brain neural stem cells (NSCs) are considered rare cells restricted to two specialised niches, the subventricular zone (SVZ) and the subgranular zone. Recent findings demonstrated that in response to injury new neurons can be generated also by parenchymal astrocytes, however the prevalence, distribution, and behaviour of these ectopic NSCs remained elusive. Consequently, the extent to which the neurogenic potential of the mature brain parenchyma differs from that of conventional neurogenic niches remains to be determined. To tackle this issue, here, we reconstructed the

…is the earliest stage in which the neural stem cells (NSCs) produced can be affected by a variety of factors, such as antibiotic toxicity. Fosfomycin (FOS) is a very reactive broad-spectrum antibiotic and is commonly prescribed for urinary tract infections (UTI). Previous data from our lab indicated a serious negative effect on NSCs when FOS was administered to rats. In this study, we aim to inves

Previous reports showed that many cognitive deficits arise in patients exhibiting symptoms of urinary tract infections (UTI) including neuropsychiatric disorders. In our laboratory, we have shown that E-coli induced UTI in adult rats caused a significant decrease in neurogenesis and impaired cognitive and memory skills. No studies have explored the mechanism of action and the effect of chronic inflammation mimicking UTI on neurogenesis and brain plasticity. Here, we aim to investigate the effect of chronic peripheral inflammation via lipopolysaccharide (LPS) instillation in the urothelium on c