A5047082571- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Nerve injury and regeneration
- Spinal Cord Injury Research
- Mesenchymal stem cell research
- MicroRNA in disease regulation
- Neurogenetic and Muscular Disorders Research
- Spinal Dysraphism and Malformations
- Single-cell and spatial transcriptomics
- Neuroscience and Neuropharmacology Research
- Zebrafish Biomedical Research Applications
- Fibroblast Growth Factor Research
- Adipose Tissue and Metabolism
- Nuclear Receptors and Signaling
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Pluripotent Stem Cells Research
- Kruppel-like factors research
- Epigenetics and DNA Methylation
- Neonatal and fetal brain pathology
- Peroxisome Proliferator-Activated Receptors
- Glioma Diagnosis and Treatment
University College London
2010-2024
Wolfson Foundation
2019-2024
The Ohio State University
2006-2008
The adult mammalian brain and spinal cord contain glial precursors that express platelet-derived growth factor receptor α subunit (PDGFRA) the NG2 proteoglycan. These “NG2 cells” descend from oligodendrocyte in perinatal CNS continue to generate myelinating oligodendrocytes gray white matter of postnatal brain. It has been proposed cells can also reactive astrocytes at sites injury or demyelination. To test this we examined fates PDGFRA/NG2 mouse during experimental autoimmune...
In the developing spinal cord, most oligodendrocyte precursors (OLPs) arise from ventral ventricular zone (VZ) under influence of Sonic Hedgehog, but a minority are generated dorsal VZ in Hedgehog-independent manner. forebrain too, OLPs both and VZ. It is not known whether dorsally ventrally derived (OL) lineage cells have different properties. We dual reporter mouse line to color code (vOLPs dOLPs) their differentiated progeny (vOLs dOLs) for functional studies. found that ∼80% OL postnatal...
New myelin-forming oligodendrocytes (OLs) are generated in the mouse central nervous system during adulthood. These adult-born OLs might augment existing population, contributing to neural plasticity, or else replace that die use (turnover). To distinguish between these alternatives, we induced genetic labeling of mature myelinating young adult mice and tracked their subsequent survival. OL survival rates were region dependent, being higher corpus callosum (∼90% over 20 months) motor cortex...
Oligodendrocyte progenitors (OPs) arise from distinct ventral and dorsal domains within the ventricular germinal zones of embryonic CNS. The functional significance, if any, these different populations is not known. Using dual-color reporter mice to distinguish ventrally dorsally derived OPs, we show that, in response focal demyelination young adult spinal cord or corpus callosum, OPs undergo enhanced proliferation, recruitment, differentiation as compared with their counterparts, making a...
Remyelination is the regenerative response to demyelination. Although oligodendrocyte progenitor established as major source of remyelinating cells, there no conclusive evidence on whether mature, differentiated oligodendrocytes can also contribute remyelination. Using two different inducible myelin-CreER mouse strains in which mature were prelabeled by expression membrane-bound Green fluorescent protein, we found that after focal spinal cord demyelination, surrounding surviving labeled did...
In the mouse embryonic forebrain, developmentally distinct oligodendrocyte progenitor cell populations and their progeny, oligodendrocytes, emerge from three regions in a spatiotemporal gradient ventral to dorsal. However, functional importance of this developmental heterogeneity is unknown. Using genetic strategy ablate dorsally derived lineage cells (OLCs), we show here that areas which OLCs normally reside adult central nervous system become populated myelinated by origin. These ectopic...
Abstract Oligodendrocyte (OL) loss and axon demyelination occur after spinal cord injury (SCI). OLs may be replaced, however, by proliferating NG2+ progenitor cells. Indeed, new have been noted in ventral white matter SCI. Since tissue adjacent to lesion cavities is exposed different mediators compared with outlying spared tissue, the authors used a rat SCI model compare NG2 cell proliferation OL genesis that closer meninges. cells proliferated throughout first week postinjury accumulated...
The NG2 proteoglycan is of general interest after spinal cord injury because it expressed by oligodendrocyte progenitors (OPCs), which contribute to central nervous system remyelination; however, may inhibit axon regeneration. We and others have examined the spatiotemporal expression (SCI). Here, we extend those observations provide a comprehensive analysis distribution, phenotype, colocalization cells with axons in clinically relevant model contusion. Because contusion models mimic majority...
Abstract Demyelination and oligodendrocyte loss following spinal cord injury (SCI) are well documented. Recently, we showed progenitor cell (OPC) accumulation robust genesis occurring along SCI lesion borders. We have since begun investigating potential mechanisms for this endogenous repair response. Here, examined ciliary neurotrophic factor (CNTF) fibroblast growth factor‐2 (FGF‐2) expression, because both factors alter proliferation differentiation increased in several CNS disorders....
Spinal cord injury is a long-lasting, debilitating condition that affects ∼250,000 people in the United States. Spontaneous functional recovery after human spinal limited because of severe axonal damage and poor regeneration. Hence, major area focus has been to preserve