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

Dimou, Leda; Simon, Christiane; Kirchhoff, Frank; Takebayashi, Hirohide; Götz, Magdalena

doi:10.1523/jneurosci.2831-08.2008

Cited by 482 publications

(627 citation statements)

References 52 publications

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“…For example, following brain ischemia due to permanent middle cerebral artery occlusion (MCAo), generation of both astrocytic and neuronal precursors from NG2 + cells was observed in adult NG2creBAC:ZEG double transgenic mice, in which enhanced green fluorescent protein (EGFP) is expressed in OPCs and their progeny, thus allowing to visualize their final phenotype [10]. However, conflicting data arise from the different transgenic mouse models employed, and the controversy around the multipotency and neurogenic potential of OPCs in vivo is still an open issue [11][12][13][14][15].…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

A new role for the P2Y-like GPR17 receptor in the modulation of multipotency of oligodendrocyte precursor cells in vitro

Boccazzi

Lecca

Marangon

et al. 2016

Purinergic Signalling

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Oligodendrocyte precursor cells (OPCs, also called NG2 cells) are scattered throughout brain parenchyma, where they function as a reservoir to replace lost or damaged oligodendrocytes, the myelin-forming cells. The hypothesis that, under some circumstances, OPCs can actually behave as multipotent cells, thus generating astrocytes and neurons as well, has arisen from some in vitro and in vivo evidence, but the molecular pathways controlling this alternative fate of OPCs are not fully understood. Their identification would open new opportunities for neuronal replace strategies, by fostering the intrinsic ability of the brain to regenerate. Here, we show that the anti-epileptic epigenetic modulator valproic acid (VPA) can promote the generation of new neurons from NG2 + OPCs under neurogenic protocols in vitro, through their initial de-differentiation to a stem cell-like phenotype that then evolves to Bhybrid^cell population, showing OPC morphology but expressing the neuronal marker βIII-tubulin and the GPR17 receptor, a key determinant in driving OPC transition towards myelinating oligodendrocytes. Under these conditions, the pharmacological blockade of the P2Y-like receptor GPR17 by cangrelor, a drug recently approved for human use, partially mimics the effects mediated by VPA thus accelerating cells' neurogenic conversion. These data show a co-localization between neuronal markers and GPR17 in vitro, and suggest that, besides its involvement in oligodendrogenesis, GPR17 can drive the fate of neural precursor cells by instructing precursors towards the neuronal lineage. Being a membrane receptor, GPR17 represents an ideal Bdruggable^target to be exploited for innovative regenerative approaches to acute and chronic brain diseases.

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Section: Electronic Supplementary Materialsmentioning

confidence: 99%

A new role for the P2Y-like GPR17 receptor in the modulation of multipotency of oligodendrocyte precursor cells in vitro

Boccazzi

Lecca

Marangon

et al. 2016

Purinergic Signalling

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“…ϩ precursors appear to have the highest capacity for proliferation in vivo after brain injury (Zaidi et al, 2004;Buffo et al, 2005;Dimou et al, 2008).…”

Section: Inhibition Of the Shh-gli Axis Reduces The Proliferating Olig2mentioning

confidence: 99%

Sonic Hedgehog Pathway Activation Is Induced by Acute Brain Injury and Regulated by Injury-Related Inflammation

et al. 2009

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The adult mammalian brain responds to injury by activating a program of cell proliferation during which many oligodendrocyte precursors, microglia, and some astrocytes proliferate. Another common response to brain injury is the induction of reactive gliosis, a process whereby dormant astrocytes undergo morphological changes and alter their transcriptional profiles. Although brain injury-induced reactive gliosis is concurrent with the proliferation of surrounding cells, a functional relationship between reactive gliosis and this cell proliferation has not been clearly demonstrated. Here, we show that the mitogen sonic hedgehog (SHH) is produced in reactive astrocytes after injury to the cerebral cortex and participates in regulating the proliferation of Olig2-expressing (Olig2 ϩ ) cells after brain injury. Using a cortical freeze injury to induce reactive gliosis in a Gli-luciferase reporter mouse, we show that the SHH pathway is maximally active 3 d after brain injury and returns to baseline levels by 14 d. SHH expression parallels Gli activation and localizes to glial fibrillary acidic protein-expressing reactive astrocytes. Inhibition of the SHH pathway with cyclopamine blocks the Gli response and significantly reduces both the proliferating and overall number of Olig2 ϩ cells in the injured cortex. To provide mechanistic insight into SHH pathway activation in astrocytes, we show that proinflammatory stimuli activate SHH-expressing reactive astrocytes, whereas inhibition of inflammation-induced reactive gliosis by macrophage depletion abolishes SHH activation after brain injury and dampens cell proliferation after injury. Our data describes a unique reactive astrocyte-based, SHH-expressing niche formed in response to injury and inflammation that regulates the proliferation of Olig2 ϩ cells.

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“…Interestingly, the mouse cortex contains also a large fraction of oligodendrocyte precursors cells that are tightly associated with neurons and do not synthesize Mbp (Trotter et al, 2010). Fate-mapping studies in the mouse showed that although these cells are mostly quiescent, they can be activated to divide and can give rise to oligodendrocytes, to neurons in the piriform cortex, and also to astrocytes (Kim et al, 2007;Dimou et al, 2008;Rivers et al, 2008;Zhao et al, 2009). These cells, which have processes that contact neurons, were variably referred to as polydendrocytes or more generally as OPCs in the mouse and rat (Wolswijk and Noble, 1989;Nishiyama et al, 1999Nishiyama et al, , 2009Hermann et al, 2010).…”

Section: Olig2 Cells In the Parenchyma Of The Telencephalonmentioning

confidence: 99%

Expression of the transcription factor Olig2 in proliferating cells in the adult zebrafish telencephalon

März

Schmidt

Rastegar

et al. 2010

Developmental Dynamics

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The telencephalon of the adult zebrafish is highly proliferative: Dividing cells are found along the entire ventricular zone and in the parenchyma. Here, we investigated the relation of proliferating cells in the telencephalic parenchyma to the oligodendrocyte lineage. We find at least three different cell types of the oligodendrocyte lineage (olig2-and sox10-positive) in the parenchyma of the telencephalon: Proliferating progenitors (PCNA-positive), including a subpopulation of slowly dividing progenitors (long term label-retaining), as well as mature oligodendrocytes (Mbp-positive) and presumptive quiescent OPCs (neither Mbppositive nor proliferating). Furthermore, in the ventricular zone (in and ventral to the RMS), two different subpopulations of olig2-positive cell populations are present. Since these ventricular olig2-positive cells do not express the oligodendrocyte marker sox10, it is not clear whether these cells indeed belong to the oligodendrocyte lineage. Taken together, we detected at least five different classes of olig2-positive cells in the telencephalon of the adult zebrafish. Developmental Dynamics 239:3336-3349,

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

Cited by 482 publications

References 52 publications

A new role for the P2Y-like GPR17 receptor in the modulation of multipotency of oligodendrocyte precursor cells in vitro

A new role for the P2Y-like GPR17 receptor in the modulation of multipotency of oligodendrocyte precursor cells in vitro

Sonic Hedgehog Pathway Activation Is Induced by Acute Brain Injury and Regulated by Injury-Related Inflammation

Expression of the transcription factor Olig2 in proliferating cells in the adult zebrafish telencephalon

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