Evidence that perinatal and adult NG2-glia are not conventional oligodendrocyte progenitors and do not depend on axons for their survival

Greenwood, Kirsty; Butt, Arthur M.

doi:10.1016/s1044-7431(03)00176-3

Cited by 58 publications

(45 citation statements)

References 47 publications

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“…It is therefore well conceivable that the Olig2-derived cells are arrested in an "immature," although postmitotic state. These NG2 ϩ glial cells could then perform specific physiological functions (Butt et al, 2002;Greenwood and Butt, 2003;Paukert and Bergles, 2006;Nishiyama, 2007;Káradó ttir et al, 2008), although it is not clear whether NG2…”

Section: Mechanisms Mediating Distinct Progeny Of Olig2mentioning

confidence: 99%

Progeny of Olig2-Expressing Progenitors in the Gray and White Matter of the Adult Mouse Cerebral Cortex

Dimou¹,

Simon²,

Kirchhoff³

et al. 2008

J. Neurosci.

478

564

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Despite their abundance, still little is known about the rather frequent, constantly proliferating progenitors spread throughout the adult mouse brain parenchyma. The majority of these progenitors express the basic-helix-loop-helix transcription factor Olig2, and their number further increases after injury. Here, we examine the progeny of this progenitor population by genetic fate mapping using tamoxifen-inducible Cre-recombination in the Olig2 locus to turn on permanent reporter gene expression in the adult brain. Consistent with Olig2 expression in proliferating NG2 ϩ progenitors, most reporter ϩ cells seen shortly after initiating recombination at adult stages incorporated BrdU and contained the proteoglycan NG2 in both the gray (GM) and the white matter (WM) of the cerebral cortex. However, at longer time points after induction, we observed profound differences in the identity of reporter ϩ cells in the WM and GM. Whereas most of the Olig2 ϩ progenitors had generated mature, myelinating oligodendrocytes in the WM, hardly any reporter ϩ cells showing mature oligodendrocyte characteristics were detectable even up to 6 months after recombination in the GM. In the GM, most reporter ϩ cells remained NG2 ϩ , even after injury, but stopped proliferating rather soon after recombination. Thus, our results demonstrate the continuous generation of mature, myelinating oligodendrocytes in the WM, whereas cells in the GM generated mostly postmitotic NG2 ϩ glia.

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Section: Mechanisms Mediating Distinct Progeny Of Olig2mentioning

confidence: 99%

Progeny of Olig2-Expressing Progenitors in the Gray and White Matter of the Adult Mouse Cerebral Cortex

Dimou¹,

Simon²,

Kirchhoff³

et al. 2008

J. Neurosci.

478

564

View full text Add to dashboard Cite

show abstract

“…77,78. However, NG2 expressing glia are distinct from OPCs or O-2A cells that give rise to oligodendrocytes during development. [79][80][81] For example, OPCs that are committed to differentiation into oligodendrocytes express the tetraspanin protein CD9, but only a minority (o1%) of adult NG2-glia express CD9. 75 Furthermore, NG2-glia in the optic nerve do not depend on axons, 80 in direct contrast to O-2A cells, which are lost following the optic nerve transection due to a 90% decrease in their proliferation.…”

Section: Atp-evoked Ca 2 þ Signalling In Physiology and Pathologymentioning

confidence: 99%

“…[79][80][81] For example, OPCs that are committed to differentiation into oligodendrocytes express the tetraspanin protein CD9, but only a minority (o1%) of adult NG2-glia express CD9. 75 Furthermore, NG2-glia in the optic nerve do not depend on axons, 80 in direct contrast to O-2A cells, which are lost following the optic nerve transection due to a 90% decrease in their proliferation. 82,83 Notwithstanding this, a population of NG2 þ OPCs gives rise to remyelinating oligodendrocyte in MS and in animal models of EAE.…”

Section: Atp-evoked Ca 2 þ Signalling In Physiology and Pathologymentioning

confidence: 99%

Functions of optic nerve glia: axoglial signalling in physiology and pathology

Butt

Pugh

Hubbard

et al. 2004

Eye

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An early concept of glial function envisaged them as passive and unexcitable structural elements, much like the connective tissues of organs in the periphery. It is now known that glia have a widespread range of physiological roles and react to all forms of pathological insult. This paper reviews the major functions of oligodendrocytes and astrocytes, the main types of glia in the optic nerve, and examines novel NG2-glia, otherwise known as oligodendrocyte progenitor cells (OPCs). The major function of oligodendrocytes is to produce the myelin sheaths that insulate CNS axons, but they also have important roles in the establishment of nodes of Ranvier, the sites of action potential propagation, and axonal integrity. Astrocytes have multiple physiological and pathological functions, including potassium homeostasis and metabolism, and reactive astrogliosis in response to CNS insults. The bulk of NG2-glia are postmitotic complex cells, distinct from OPCs, and respond to any insult to the CNS by a rapid and stereotypic injury response. This may be their primary unction, but NG2-glia, or a subpopulation of NG2-expressing adult OPCs, also provide remyelinating oligodendrocytes following demyelination. Oligodendrocytes, astrocytes, and NG2-glia all contact axons at nodes of Ranvier and respond to glutamate, ATP, and potassium released during axonal electrical activity. Glutamate and ATP evoke calcium signalling in optic nerve glia and have dual roles in physiology and pathology, coupling glial functions to axonal activity during normal activity, but enhanced activation induces an injury response, as seen following injury, demyelination, and ischaemia.

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Section: Introductionmentioning

confidence: 99%

“…However, the identity of these cells needs further consideration because the specificity of NG2 as an OPC marker becomes increasingly questionable. Current work suggests that NG2 cells comprise a distinct, heterogeneous type of neuroglial cells (Nishiyama et al, 2002;Stallcup, 2002;Greenwood and Butt, 2003;Aguirre et al, 2004;Peters, 2004).Using transgenic mice expressing green fluorescent protein under control of the human GFAP promoter (hGFAP/EGFP mice), we have recently reported a co-existence of two types of glial cells in the hippocampus, distinguishable from each other by mutually exclusive expression of glutamate transporters (GluT type) and ionotropic glutamate receptors (GluR cells). GluT type cells were extensively coupled via gap junctions and contacted blood vessels, thus matching properties of classical astrocytes.…”

mentioning

confidence: 99%

Synaptic transmission onto hippocampal glial cells with hGFAP promoter activity

Jabs

Pivneva

Hüttmann

et al. 2005

Journal of Cell Science

141

158

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IntroductionRecent work on glial cell physiology has disclosed that these cells are much more actively involved in brain information processing than hitherto thought. This new insight stimulates a new view according to which the active brain has to be regarded as an integrated circuit of interactive neurons and glial cells. Astrocytes in particular are now regarded as direct communication partners of neurons, by dynamically interacting with synapses through the uptake and release of neurotransmitters and receptor-mediated intracellular Ca 2+ signalling (for reviews, see Haydon, 2001;Newman, 2003;Volterra and Steinhäuser, 2004;Schipke and Kettenmann, 2004). Intriguingly, a distinct subset of glial cells in the hippocampus was reported to receive direct synaptic input from glutamatergic and GABAergic neurons. These glial cells expressed the proteoglycan, NG2, and on this basis were regarded as oligodendrocyte precursor cells (OPCs) (Bergles et al., 2000;Lin and Bergles, 2003). However, the identity of these cells needs further consideration because the specificity of NG2 as an OPC marker becomes increasingly questionable. Current work suggests that NG2 cells comprise a distinct, heterogeneous type of neuroglial cells (Nishiyama et al., 2002;Stallcup, 2002;Greenwood and Butt, 2003;Aguirre et al., 2004;Peters, 2004).Using transgenic mice expressing green fluorescent protein under control of the human GFAP promoter (hGFAP/EGFP mice), we have recently reported a co-existence of two types of glial cells in the hippocampus, distinguishable from each other by mutually exclusive expression of glutamate transporters (GluT type) and ionotropic glutamate receptors (GluR cells). GluT type cells were extensively coupled via gap junctions and contacted blood vessels, thus matching properties of classical astrocytes. By contrast, GluR cells lacked junctional coupling and did not enwrap capillaries (Matthias et al., 2003;Wallraff et al., 2004). Moreover, GluR cells co-expressed S100␤, a common astrocyte marker, NG2, as well as neuronal genes, and hence escaped classification into neurons, astrocytes, or oligodendrocytes.Here we used the hGFAP/EGFP transgenic animal to identify distinct types of glial cells in live slices. We combined ultrastructural analysis and post-recording immunocytochemistry to test whether the two populations of hGFAP/EGFP-positive glial cells in the hippocampus receive synaptic input. Electron microscopic inspection identified synapse-like structures with EGFP-positive postsynaptic compartments. Patch clamp recordings revealed stimulus- Stimulus-correlated and spontaneous responses were quantitatively analysed by ascertaining amplitude distributions, failure rates, kinetics as well as pharmacological properties. The data demonstrate that GABAergic and glutamatergic neurons directly synapse onto GluR cells and suggest a low number of neuronal release sites. These data demonstrate that a distinct type of glial cells is integrated into the synaptic circuit of the hippocampus, extending the finding that synaps...

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Evidence that perinatal and adult NG2-glia are not conventional oligodendrocyte progenitors and do not depend on axons for their survival

Cited by 58 publications

References 47 publications

Progeny of Olig2-Expressing Progenitors in the Gray and White Matter of the Adult Mouse Cerebral Cortex

Progeny of Olig2-Expressing Progenitors in the Gray and White Matter of the Adult Mouse Cerebral Cortex

Functions of optic nerve glia: axoglial signalling in physiology and pathology

Synaptic transmission onto hippocampal glial cells with hGFAP promoter activity

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