A5036857596- Neurogenesis and neuroplasticity mechanisms
- Developmental Biology and Gene Regulation
- Axon Guidance and Neuronal Signaling
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurobiology and Insect Physiology Research
- Olfactory and Sensory Function Studies
- Congenital heart defects research
- Microtubule and mitosis dynamics
- Genetics and Neurodevelopmental Disorders
- Chromatin Remodeling and Cancer
- Cancer-related Molecular Pathways
- Hedgehog Signaling Pathway Studies
- Neurological Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Congenital Ear and Nasal Anomalies
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Biochemical Analysis and Sensing Techniques
- Neonatal and fetal brain pathology
- Genomic variations and chromosomal abnormalities
- Nerve injury and regeneration
Institut du Cerveau
2013-2025
Inserm
2013-2024
Sorbonne Université
2013-2024
Centre National de la Recherche Scientifique
2013-2024
Pitié-Salpêtrière Hospital
2009-2024
Assistance Publique – Hôpitaux de Paris
2015-2024
Université Paris Cité
2014
NTL Institute for Applied Behavioral Science
2011
University of Zurich
2009
National Hospital for Neurology and Neurosurgery
2004-2008
Proneural genes such as Ascl1 are known to promote cell cycle exit and neuronal differentiation when expressed in neural progenitor cells. The mechanisms by which proneural activate neurogenesis--and, particular, the that they regulate--however, mostly unknown. We performed a genome-wide characterization of transcriptional targets embryonic brain stem cultures location analysis expression profiling embryos overexpressing or mutant for Ascl1. wide range molecular cellular functions...
The generation of neurons by progenitor cells involves the tight coordination multiple cellular activities, including cell cycle exit, initiation neuronal differentiation, and migration. mechanisms that integrate these different events into a coherent developmental program are not well understood. Here we show cyclin-dependent kinase inhibitor p27 Kip1 plays an important role in neurogenesis mouse cerebral cortex promoting differentiation radial migration cortical projection neurons....
The neural bHLH genes Mash1 and Ngn2 are expressed in complementary populations of progenitors the central peripheral nervous systems. Here, we have systematically compared activities two during development by generating replacement mutations mice which coding sequences were swapped. Using this approach, demonstrate that has capacity to respecify identity neuronal normally derived from -expressing dorsal telencephalon ventral spinal cord. In contrast, misexpression does not result any overt...
Little is known of the intracellular machinery that controls motility newborn neurons. We have previously shown proneural protein Neurog2 promotes migration nascent cortical neurons by inducing expression atypical Rho GTPase Rnd2. Here, we show another factor, Ascl1, neuronal in cortex through direct regulation a second Rnd family member, Rnd3. Both Rnd2 and Rnd3 promote inhibiting RhoA signaling, but they control distinct steps migratory process, multipolar to bipolar transition...
The bHLH (basic helix-loop-helix) transcription factor Mash1 is best known for its role in the regulation of neurogenesis. However, also expressed oligodendrocyte precursors and has recently been shown to promote generation oligodendrocytes cell culture, suggesting that it may regulate oligodendrogenesis as well. Here, we show developing ventral forebrain, by a subset (OPCs) soon they are generated ventricular zone. Using reporter mice, demonstrate OPCs both embryonic postnatal forebrain...
During development, the three major neural cell lineages, neurons, oligodendrocytes and astrocytes, differentiate in specific temporal orders at topologically defined positions. How timing position of their generation are coordinately regulated remains poorly understood. Here, we provide evidence that transcription factors Pax6, Olig2 Nkx2.2 (Nkx2-2), which define positional identity multipotent progenitors early also play crucial roles controlling neurogenesis gliogenesis developing ventral...
The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how interacts with chromatin landscape regulate when promoting differentiation. We find that binding occurs mostly at distal enhancers is associated activation transcription. Surprisingly, accessibility its sites neural stem/progenitor cells remains largely unchanged throughout...
The corpus callosum (CC) is the main pathway responsible for interhemispheric communication. CC agenesis associated with numerous human pathologies, suggesting that a range of developmental defects can result in abnormalities this structure. Midline glial cells are known to play role development, but we here show two transient populations midline neurons also make major contributions formation commissure. We report these neuronal enter prior arrival callosal pioneer axons. Using combination...
Oligodendrocytes are the myelin-forming cells of CNS. They differentiate from oligodendrocyte precursor (OPCs) that produced progenitors throughout life but more actively during neonatal period and in response to demyelinating insults. An accurate regulation oligodendrogenesis is required generate oligodendrocytes these developmental or repair processes. We hypothesized this implicates transcription factors, which expressed by OPCs and/or their progenitors. Ascl1/Mash1 a proneural factor...
Neural stem cells (NSCs) continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that hippocampal express vascular endothelial growth factor receptor (VEGFR) 3 and its ligand VEGF-C, which activates enter cell cycle generate Hippocampal neurogenesis impaired by conditional deletion Vegfr3 in...
Significance Oligodendrocyte precursor cells (OPCs) constitute the main proliferative in adult brain and deregulation of OPC proliferation-differentiation balance results either glioma formation or defective (re)myelination. Mutations chromatin remodelers CHD7 CHD8 are cause CHARGE syndrome some autism spectrum disorders (ASD). Here we show that Chd7 protects OPCs from apoptosis by closing gene repression p53 , while induces opening activation OPC-differentiation regulators. is, however,...
The dentate gyrus (DG) of the hippocampus has a central role in learning and memory adult rodents. DG is generated soon after birth, although new neurons continue to be throughout life. proneural factors Mash1 (Ascl1) neurogenin 2 (Ngn2) are expressed during formation but their development this structure not yet been addressed. Here, we show that Ngn2 essential for DG. mutant mice have fewer progenitors these cells present defects neuronal differentiation. By contrast, normal at loss both...
Development of oligodendrocytes, myelin-forming glia in the central nervous system (CNS), proceeds on a protracted schedule. Specification oligodendrocyte progenitors (OLPs) begins early development, whereas their terminal differentiation occurs at late embryonic and postnatal periods. How these distinct steps are controlled remains unclear. Our previous study demonstrated an important role helix-loop-helix (HLH) transcription factor Ascl1 generation OLPs developing spinal cord. Here, we...
Abstract Neuroprotective, anti-inflammatory, and remyelinating properties of androgens are well-characterized in demyelinated male mice men suffering from multiple sclerosis. However, androgen effects mediated by the receptor (AR), have been only poorly studied females who make low levels. Here, we show a predominant microglial AR expression lesions female women with sclerosis, but virtually undetectable animals In mice, estrogens act synergistic way while drive microglia response towards...
During Drosophila neural development, neuroblasts delaminate from the neuroectoderm of each hemisegment in a stereotypic orthogonal array five rows and three columns (ventral, intermediate, dorsal). Prevailing evidence indicates that individual neuroblast fate is determined by domain-specific expression genes along dorsoventral anteroposterior axis. Here, we analyze role Vnd, NK-2 homeodomain protein, expressed initially ventral adjacent to midline, patterning neuroblasts. We show vnd null...
The ventricular-subventricular zone (V-SVZ) is the largest neurogenic region of postnatal forebrain, containing neural stem cells (NSCs) that emerge from both embryonic pallium and subpallium. Despite this dual origin, glutamatergic neurogenesis declines rapidly after birth, while GABAergic persists throughout life. We performed single-cell RNA sequencing dorsal V-SVZ for unraveling mechanisms leading to pallial lineage germinal activity silencing. show NSCs enter a state deep quiescence,...
Abstract Little is known of the transcription factors expressed by adult neural progenitors produced in hippocampal neurogenic niche. Here, we study expression proneural basic helix‐loop‐helix (bHLH) factor Neurogenin‐2 (Ngn2) hippocampus. We have characterized pattern Ngn2 hippocampus using immunostaining for protein and a Ngn2‐green fluorescent (GFP) reporter mouse strain. A significant proportion Ngn2‐expressing cells were mitotically active. Ngn2‐GFP was restricted to subgranular zone...
Glia constitute the majority of cells in mammalian central nervous system and are crucial for neurological function. However, there is an incomplete understanding molecular control glial cell development. We find that transcription factor Ascl1 (Mash1), which best known its role neurogenesis, also functions both astrocyte oligodendrocyte lineages arising mouse spinal cord at late embryonic stages. Clonal fate mapping vivo reveals heterogeneity Ascl1-expressing progenitors shows defines...