defining the neuroepithelial domain that gives rise to MNs and, in combination with the neurogeni... more defining the neuroepithelial domain that gives rise to MNs and, in combination with the neurogenic bHLH protein Neurogenin2 (Ngn2), is required to specify MN fate. How do these precursors suddenly switch from neuron to OLP production? The studies by Mizuguchi et al. (2001) and Novitch et al. (2001) together with the accompanying article by Zhou In the developing spinal cord, neuroepithelial precur-et al. (2001 [this issue of Neuron]) suggest an elegant sors at different positions along the dorsal-ventral axis mechanism. A temporal shift of gene expression pat-generate distinct neuronal and glial subtypes. For ex-terns in the ventral cord provides Olig2 with successive ample, one group of ventral precursors generates neu-regulatory partners, first Ngn1/2 and Pax6, and then rons followed by oligodendrocytes. A spate of recent Nkx2.2. In collaboration with these factors, Olig2 first articles, including several in this issue of Neuron, are specifies MNs, then OLPs. devoted to the mechan...
Using in situ hybridization, we have visualized cells in the rat central nervous system (CNS) tha... more Using in situ hybridization, we have visualized cells in the rat central nervous system (CNS) that contain mRNA encoding the platelet-derived growth factor alpha receptor (PDGF-alpha R). After embryonic day 16 (E16), PDGF-alpha R mRNA appears to be expressed by a subset of glial cells, but not by neurons. The temporal and spatial distribution of PDGF-alpha R+ cells, together with 125I-PDGF binding studies on subsets of glial cells in vitro, suggests that PDGF-alpha R may be expressed predominantly, or exclusively, by cells of the oligodendrocyte-type-2 astrocyte (O-2A) lineage. This conclusion is supported by the fact that the numbers of PDGF-alpha R+ cells in developing and adult optic nerves correlate well with independent estimates of the number of O-2A progenitor cells in the nerve at equivalent ages. Small numbers of PDGF-alpha R+ cells are present in the brain at E16, at which time they are found outside the subventricular germinal zones, suggesting that these cells do not exp...
During rat embryogenesis, PDGF alpha receptor (PDGF-alpha R) mRNA is expressed in the ventral hal... more During rat embryogenesis, PDGF alpha receptor (PDGF-alpha R) mRNA is expressed in the ventral half of the spinal cord in two longitudinal columns, one each side of the central canal. Initially, these columns are only two cells wide but the cells subsequently appear to proliferate and disseminate throughout the spinal cord. Our previous studies of PDGF-alpha R expression in the developing CNS suggested that PDGF-alpha R may be a useful marker of the oligodendrocyte lineage in situ. The data presented here complement those studies and lead us to propose that the earliest oligodendrocyte precursors in the spinal cord originate in a very restricted region of the ventricular zone during a brief window of time around embryonic day 14 (E14). In the embryonic brain, migrating PDGF-alpha R+ cells appear to originate in a localized germinal zone in the ventral diencephalon (beneath the foramen of Monro). Our data demonstrate that gene expression and cell fate can be regulated with exquisite s...
We show that the G protein-coupled receptor GPR37-like 1 (GPR37L1) is expressed in most astrocyte... more We show that the G protein-coupled receptor GPR37-like 1 (GPR37L1) is expressed in most astrocytes and some oligodendrocyte precursors in the mouse central nervous system. This contrasts with GPR37, which is mainly in mature oligodendrocytes. Comparison of wild type and Gpr37l1(-/-) mice showed that loss of GPR37L1 did not affect the input resistance or resting potential of astrocytes or neurons in the hippocampus. However, GPR37L1-mediated signalling inhibited astrocyte glutamate transporters and - surprisingly, given its lack of expression in neurons - reduced neuronal NMDA receptor (NMDAR) activity during prolonged activation of the receptors as occurs in ischemia. This effect on NMDAR signalling was not mediated by a change in the release of D-serine or TNF-α, two astrocyte-derived agents known to modulate NMDAR function. After middle cerebral artery occlusion, Gpr37l1 expression was increased around the lesion. Neuronal death was increased by ∼40% in Gpr37l1(-/-) brain compared...
Molecular Signaling and Regulation in Glial Cells, 1997
Oligodendrocytes, the myelinating cells of the CNS, develop from glial progenitor cells known as ... more Oligodendrocytes, the myelinating cells of the CNS, develop from glial progenitor cells known as 0-2A progenitors (for reviews see 1,2 and 3). 0-2A progenitor cells are so-called because they can differentiate into either oligodendrocytes or type-2 astrocytes in vitro: in medium containing low (≤ 0.5%) fetal calf serum (FCS) they differentiate into oligodendrocytes whereas in 10% FCS they differentiate into type-2 astrocytes (4). 0-2A progenitors and their differentiated progeny can be distinguished in vitro by morphology and by their characteristic antigenic phenotypes. 0-2A progenitors often have a bipolar morphology and label with monoclonal antibody A2B5 (5), which recognizes a specific set of gangliosides, and with antibodies to the NG2 chondroitin sulphate (6). As they mature, 0-2A progenitors become multi-polar, their proliferative and migratory properties change (7 and 8) and they start to express sulphatide and other related antigens that are recognized by monoclonal antibody 04 (9). Differentiated oligodendrocytes have a complex, process-bearing morphology and label specifically with antibodies against galactocerebroside (GC) (10). Type-2 astrocytes are process-bearing cells in vitro that label with antibodies against the glial fibrillary acidic protein (GFAP). After they differentiate, oligodendrocytes lose the A2B5 antigen whereas type-2 astrocytes retain it. The oligodendrocyte differentiation pathway seems to be the default behaviour for 0-2A progenitors because a single progenitor cell differentiates into an oligodendrocyte if it is cultured on its own in defined, low-serum medium in the absence of other cells (11). It is not known what the active ingredient in FCS is that can induce type-2 astrocyte differentiation in vitro, but the activity can be mimicked by pure ciliary neurotrophic factor (CNTF) in collaboration with uncharacterized extracellular matrix components secreted by cultures of cortical astrocytes (12). Despite careful searching, there is still no definitive evidence for the existence of cells with the antigenic phenotype of type-2 astrocytes in vivo (13). Perhaps type-2 astrocytes will eventually turn up in a restricted region(s) of the CNS or under certain pathological conditions. For the present, however, we regard 0-2A progenitors as dedicated oligodendrocyte progenitors in vivo, but retain the prefix 0-2A as a reminder of their differentiation potential in vitro. Figure 1 shows a diagram of the life history of an oligodendrocyte.
Philosophical Transactions of the Royal Society B: Biological Sciences, 2008
All the neurons and glial cells of the central nervous system are generated from the neuroepithel... more All the neurons and glial cells of the central nervous system are generated from the neuroepithelial cells in the walls of the embryonic neural tube, the ‘embryonic neural stem cells’. The stem cells seem to be equivalent to the so-called ‘radial glial cells’, which for many years had been regarded as a specialized type of glial cell. These radial cells generate different classes of neurons in a position-dependent manner. They then switch to producing glial cells (oligodendrocytes and astrocytes). It is not known what drives the neuron–glial switch, although downregulation of pro-neural basic helix–loop–helix transcription factors is one important step. This drives the stem cells from a neurogenic towards a gliogenic mode. The stem cells then choose between developing as oligodendrocytes or astrocytes, of which there might be intrinsically different subclasses. This review focuses on the different extracellular signals and intracellular responses that influence glial generation and ...
defining the neuroepithelial domain that gives rise to MNs and, in combination with the neurogeni... more defining the neuroepithelial domain that gives rise to MNs and, in combination with the neurogenic bHLH protein Neurogenin2 (Ngn2), is required to specify MN fate. How do these precursors suddenly switch from neuron to OLP production? The studies by Mizuguchi et al. (2001) and Novitch et al. (2001) together with the accompanying article by Zhou In the developing spinal cord, neuroepithelial precur-et al. (2001 [this issue of Neuron]) suggest an elegant sors at different positions along the dorsal-ventral axis mechanism. A temporal shift of gene expression pat-generate distinct neuronal and glial subtypes. For ex-terns in the ventral cord provides Olig2 with successive ample, one group of ventral precursors generates neu-regulatory partners, first Ngn1/2 and Pax6, and then rons followed by oligodendrocytes. A spate of recent Nkx2.2. In collaboration with these factors, Olig2 first articles, including several in this issue of Neuron, are specifies MNs, then OLPs. devoted to the mechan...
Using in situ hybridization, we have visualized cells in the rat central nervous system (CNS) tha... more Using in situ hybridization, we have visualized cells in the rat central nervous system (CNS) that contain mRNA encoding the platelet-derived growth factor alpha receptor (PDGF-alpha R). After embryonic day 16 (E16), PDGF-alpha R mRNA appears to be expressed by a subset of glial cells, but not by neurons. The temporal and spatial distribution of PDGF-alpha R+ cells, together with 125I-PDGF binding studies on subsets of glial cells in vitro, suggests that PDGF-alpha R may be expressed predominantly, or exclusively, by cells of the oligodendrocyte-type-2 astrocyte (O-2A) lineage. This conclusion is supported by the fact that the numbers of PDGF-alpha R+ cells in developing and adult optic nerves correlate well with independent estimates of the number of O-2A progenitor cells in the nerve at equivalent ages. Small numbers of PDGF-alpha R+ cells are present in the brain at E16, at which time they are found outside the subventricular germinal zones, suggesting that these cells do not exp...
During rat embryogenesis, PDGF alpha receptor (PDGF-alpha R) mRNA is expressed in the ventral hal... more During rat embryogenesis, PDGF alpha receptor (PDGF-alpha R) mRNA is expressed in the ventral half of the spinal cord in two longitudinal columns, one each side of the central canal. Initially, these columns are only two cells wide but the cells subsequently appear to proliferate and disseminate throughout the spinal cord. Our previous studies of PDGF-alpha R expression in the developing CNS suggested that PDGF-alpha R may be a useful marker of the oligodendrocyte lineage in situ. The data presented here complement those studies and lead us to propose that the earliest oligodendrocyte precursors in the spinal cord originate in a very restricted region of the ventricular zone during a brief window of time around embryonic day 14 (E14). In the embryonic brain, migrating PDGF-alpha R+ cells appear to originate in a localized germinal zone in the ventral diencephalon (beneath the foramen of Monro). Our data demonstrate that gene expression and cell fate can be regulated with exquisite s...
We show that the G protein-coupled receptor GPR37-like 1 (GPR37L1) is expressed in most astrocyte... more We show that the G protein-coupled receptor GPR37-like 1 (GPR37L1) is expressed in most astrocytes and some oligodendrocyte precursors in the mouse central nervous system. This contrasts with GPR37, which is mainly in mature oligodendrocytes. Comparison of wild type and Gpr37l1(-/-) mice showed that loss of GPR37L1 did not affect the input resistance or resting potential of astrocytes or neurons in the hippocampus. However, GPR37L1-mediated signalling inhibited astrocyte glutamate transporters and - surprisingly, given its lack of expression in neurons - reduced neuronal NMDA receptor (NMDAR) activity during prolonged activation of the receptors as occurs in ischemia. This effect on NMDAR signalling was not mediated by a change in the release of D-serine or TNF-α, two astrocyte-derived agents known to modulate NMDAR function. After middle cerebral artery occlusion, Gpr37l1 expression was increased around the lesion. Neuronal death was increased by ∼40% in Gpr37l1(-/-) brain compared...
Molecular Signaling and Regulation in Glial Cells, 1997
Oligodendrocytes, the myelinating cells of the CNS, develop from glial progenitor cells known as ... more Oligodendrocytes, the myelinating cells of the CNS, develop from glial progenitor cells known as 0-2A progenitors (for reviews see 1,2 and 3). 0-2A progenitor cells are so-called because they can differentiate into either oligodendrocytes or type-2 astrocytes in vitro: in medium containing low (≤ 0.5%) fetal calf serum (FCS) they differentiate into oligodendrocytes whereas in 10% FCS they differentiate into type-2 astrocytes (4). 0-2A progenitors and their differentiated progeny can be distinguished in vitro by morphology and by their characteristic antigenic phenotypes. 0-2A progenitors often have a bipolar morphology and label with monoclonal antibody A2B5 (5), which recognizes a specific set of gangliosides, and with antibodies to the NG2 chondroitin sulphate (6). As they mature, 0-2A progenitors become multi-polar, their proliferative and migratory properties change (7 and 8) and they start to express sulphatide and other related antigens that are recognized by monoclonal antibody 04 (9). Differentiated oligodendrocytes have a complex, process-bearing morphology and label specifically with antibodies against galactocerebroside (GC) (10). Type-2 astrocytes are process-bearing cells in vitro that label with antibodies against the glial fibrillary acidic protein (GFAP). After they differentiate, oligodendrocytes lose the A2B5 antigen whereas type-2 astrocytes retain it. The oligodendrocyte differentiation pathway seems to be the default behaviour for 0-2A progenitors because a single progenitor cell differentiates into an oligodendrocyte if it is cultured on its own in defined, low-serum medium in the absence of other cells (11). It is not known what the active ingredient in FCS is that can induce type-2 astrocyte differentiation in vitro, but the activity can be mimicked by pure ciliary neurotrophic factor (CNTF) in collaboration with uncharacterized extracellular matrix components secreted by cultures of cortical astrocytes (12). Despite careful searching, there is still no definitive evidence for the existence of cells with the antigenic phenotype of type-2 astrocytes in vivo (13). Perhaps type-2 astrocytes will eventually turn up in a restricted region(s) of the CNS or under certain pathological conditions. For the present, however, we regard 0-2A progenitors as dedicated oligodendrocyte progenitors in vivo, but retain the prefix 0-2A as a reminder of their differentiation potential in vitro. Figure 1 shows a diagram of the life history of an oligodendrocyte.
Philosophical Transactions of the Royal Society B: Biological Sciences, 2008
All the neurons and glial cells of the central nervous system are generated from the neuroepithel... more All the neurons and glial cells of the central nervous system are generated from the neuroepithelial cells in the walls of the embryonic neural tube, the ‘embryonic neural stem cells’. The stem cells seem to be equivalent to the so-called ‘radial glial cells’, which for many years had been regarded as a specialized type of glial cell. These radial cells generate different classes of neurons in a position-dependent manner. They then switch to producing glial cells (oligodendrocytes and astrocytes). It is not known what drives the neuron–glial switch, although downregulation of pro-neural basic helix–loop–helix transcription factors is one important step. This drives the stem cells from a neurogenic towards a gliogenic mode. The stem cells then choose between developing as oligodendrocytes or astrocytes, of which there might be intrinsically different subclasses. This review focuses on the different extracellular signals and intracellular responses that influence glial generation and ...
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Papers by Nigel Pringle