- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Pluripotent Stem Cells Research
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Axon Guidance and Neuronal Signaling
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Tissue Engineering and Regenerative Medicine
- Hedgehog Signaling Pathway Studies
- Cancer-related Molecular Pathways
- Genetics, Aging, and Longevity in Model Organisms
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Telomeres, Telomerase, and Senescence
- Adipose Tissue and Metabolism
- Prenatal Screening and Diagnostics
- Renal and related cancers
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- Nerve injury and regeneration
- Hair Growth and Disorders
- Genetic Mapping and Diversity in Plants and Animals
University of Padua
2025
Universitat de València
2014-2024
National Center for Genetic Engineering and Biotechnology
2024
Instituto de Biomedicina de Valencia
2021-2024
Biomedical Research Networking Center on Neurodegenerative Diseases
2010-2023
University of Cambridge
2011-2018
StemCells (United States)
2017
Interactions of adult neural stem cells (NSCs) with supportive vasculature appear critical for their maintenance and function, although the molecular details are still under investigation. Neurotrophin (NT)-3 belongs to NT family trophic factors, best known effects in promoting neuronal survival. Here we show that NT-3 produced secreted by endothelial brain choroid plexus capillaries is required quiescence long-term NSCs mouse subependymal niche. Uptake from irrigating cerebrospinal fluid...
Proliferation in the subependymal zone (SEZ) and neurogenesis olfactory bulb decline forebrain of telomerase-deficient mice. The present work reveals additional effects telomere shortening on neuronal differentiation, as adult multipotent progenitors with critically short telomeres yield reduced numbers neurons that, furthermore, exhibit underdeveloped neuritic arbors. Genetic data indicate that tumor suppressor protein p53 not only mediates adverse attrition proliferation self-renewal but...
Chromosome integrity is essential for cell viability and, therefore, highly proliferative types require active telomere elongation mechanisms to grow indefinitely. Consistently, deletion of telomerase activity in a genetically modified mouse strain results growth impairments all populations analyzed so far. We show that attrition dramatically impairs the vitro proliferation adult neural stem cells (NSCs) isolated from subventricular zone (SVZ) telomerase-deficient mice. Reduced postnatal...
Two known germinal zones continue to generate new neurons and glia in the adult mammalian brain: subventricular zone (SVZ), lining lateral walls of ventricle, subgranular dentate gyrus. Here we describe a region will refer as subcallosal (SCZ). The SCZ is caudal extension SVZ that no longer associated an open ventricle. It lies between hippocampus corpus callosum. Cells isolated from cultured neurospheres behave neural stem cells vitro. Using electron light microscopy, cell types present...
Abstract Genomic imprinting is implicated in the control of gene dosage neurogenic niches. Here we address importance Igf2 for murine adult neurogenesis subventricular zone (SVZ) and subgranular (SGZ) hippocampus vivo . In SVZ, paracrine IGF2 a cerebrospinal fluid endothelial-derived factor requiring biallelic expression, with mutants having reduced activation stem cell pool impaired olfactory bulb neurogenesis. contrast, imprinted acting as an autocrine expressed neural cells (NSCs) solely...
Neonatal survival in mammals is crucially dependent upon maintenance of body temperature. temperature largely maintained by thermogenesis brown adipose tissue (BAT). BAT develops perinatally mice requiring integration adipogenic and thermoregulatory gene pathways. We describe a regulatory mutation the imprinted cluster on mouse chromosome 12 resulting early postnatal lethality. Maternal inheritance this impairs ability young to maintain While mechanisms perinatal development are well...
Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance and obesity, as well progressive dysfunction. Recent animal studies have underscored the importance of hepatic growth hormone (GH) signaling in development NAFLD. The imprinted Delta-like homolog 1 (Dlk1)/preadipocyte factor (Pref1) gene encodes a complex protein producing both circulating membrane-tethered isoforms whose expression dosage functionally important because even modest elevation during embryogenesis...
Members of the cyclin-dependent kinase (CDK)-inhibitory protein (CIP)/kinase-inhibitory (KIP) family inhibitors regulate proliferation and cell cycle exit mammalian cells. In adult brain, CIP/KIP p27(kip1) has been related to regulation intermediate progenitor cells located in neurogenic niches. Here, we uncover a novel function hippocampus as dual regulator stem quiescence cell-cycle immature neurons. vivo, is detected radial expressing SOX2 newborn neurons dentate gyrus. vitro, Cdkn1b gene...
Physical exercise has positive effects on cognition, but very little is known about the inheritance of these to sedentary offspring and mechanisms involved. Here, we use a patrilineal design in mice test transmission from same father (before or after training) different fathers compare sedentary- runner-father progenies. Behavioral, stereological, whole-genome sequence analyses reveal that paternal cognition improvement inherited by offspring, along with increased adult neurogenesis, greater...
Genomic imprinting is an epigenetic mechanism that drives monoallelic gene expression depending on parental origin. Loss of (LOI) associated with human disorders, fetal development, and cancer progression. Imprinted genes, organized in clusters, are regulated by methylation at imprint control regions (ICRs), differentially methylated (DMRs) between chromosomes. Somatic cell reprogramming into induced pluripotent stem cells (iPSCs) a valuable tool for studying pluripotency holds promise...
Abstract Ten-eleven-translocation (TET) proteins catalyze DNA hydroxylation, playing an important role in demethylation of mammals. Remarkably, although hydroxymethylation levels are high the mouse brain, potential TET adult neurogenesis is unknown. We show here that a non-catalytic action TET3 essentially required for maintenance neural stem cell (NSC) pool subventricular zone (SVZ) niche by preventing premature differentiation NSCs into non-neurogenic astrocytes. This occurs through direct...
ABSTRACT Adult neurogenesis is supported by multipotent neural stem cells (NSCs) with unique properties and growth requirements. NSCs constitute a reversibly quiescent cell population that can be activated extracellular signals from the microenvironment in which they reside vivo. Although genomic imprinting plays role adult through dose regulation of some relevant signals, roles many imprinted genes process remain elusive. Insulin-like factor 2 (IGF2) encoded an gene contributes to NSC...
Abstract Insulin is one of the standard components used to culture primary neurospheres. Although it stimulates growth different types cells, effects insulin on adult neural stem cells (NSCs) have not been well characterized. Here, we reveal that proliferation, but survival or self-renewal, NSCs. This effect mediated by receptor substrate 2 (IRS2) and subsequent activation protein kinase B (or Akt), leading increased activity G1-phase cyclin-dependent 4 (Cdk4) cell cycle progression....
Significance Generation of new neurons occurs normally in the adult brain two locations: subventricular zone (SVZ) walls lateral ventricles and subgranular (SGZ) dentate gyrus (DG) hippocampus. Neurogenesis hippocampus has been implicated cognitive functions such as learning, memory, recovery stress response. Imprinted genes are highly prevalent have developmental important functions. Genetic deletion imprinted gene Dlk1 from either parental allele shows that DLK1 is a key mediator...