NG2-Glia from Pallial Progenitors Produce the Largest Clonal Clusters of the Brain: Time Frame of Clonal Generation in Cortex and Olfactory Bulb

García-Marqués, Jorge; Nuñez‐Llaves, Raúl; López‐Mascaraque, Laura

doi:10.1523/jneurosci.3060-13.2014

Cited by 37 publications

(54 citation statements)

References 52 publications

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“…NG2-glia are highly proliferative and have been shown to produce large clones containing hundreds of cells (Garcia-Marques, Nunez-Llaves, & Lopez-Mascaraque, 2014). Similarly, we observed that the largest clones of Confetti-marked cells were positive for the OL-lineage specific marker SOX10 (Fig.…”

Section: Resultsmentioning

confidence: 99%

ASCL1 regulates proliferation of NG2‐glia in the embryonic and adult spinal cord

Kelenis

Hart

Edwards-Fligner

et al. 2018

Glia

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NG2‐glia are highly proliferative oligodendrocyte precursor cells (OPCs) that are widely distributed throughout the central nervous system (CNS). During development, NG2‐glia predominantly differentiate into oligodendrocytes (OLs) to myelinate axon fibers, but they can also remain as OPCs persisting into the mature CNS. Interestingly, NG2‐glia in the gray matter (GM) are intrinsically different from those in the white matter (WM) in terms of proliferation, differentiation, gene expression, and electrophysiological properties. Here we investigate the role of the transcriptional regulator, ASCL1, in controlling NG2‐glia distribution and development in the GM and WM. In the spinal cord, ASCL1 levels are higher in WM NG2‐glia than those in the GM. This differential level of ASCL1 in WM and GM NG2‐glia is maintained into adult stages. Long‐term clonal lineage analysis reveals that the progeny of single ASCL1+ oligodendrocyte progenitors (OLPs) and NG2‐glia are primarily restricted to the GM or WM, even though they undergo extensive proliferation to give rise to large clusters of OLs in the postnatal spinal cord. Conditional deletion of Ascl1 specifically in NG2‐glia in the embryonic or adult spinal cord resulted in a significant reduction in the proliferation but not differentiation of these cells. These findings illustrate that ASCL1 is an intrinsic regulator of the proliferative property of NG2‐glia in the CNS.

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Section: Resultsmentioning

confidence: 99%

ASCL1 regulates proliferation of NG2‐glia in the embryonic and adult spinal cord

Kelenis

Hart

Edwards-Fligner

et al. 2018

Glia

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“…4A), similar to the tracing result using PdgfαR-Cre ER / Rosa26YFP (17). Furthermore, a most recent report with a StarTrack-labeled pallial NG2 population suggested that the SVZoriginated NG2 progenitors, although giving rise to the largest clonal oligodendrocyte clusters in the CTX and olfactory bulb, lack astroglial potential in vivo (27). This indicated that NG2…”

Section: Postnatal Svz Gfapmentioning

confidence: 99%

Spatiotemporally different origins of NG2 progenitors produce cortical interneurons versus glia in the mammalian forebrain

Tsoa

Coskun

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The studies on the exact lineage composition of NG2 expressing progenitors in the forebrain have been controversial. A number of studies have revealed the heterogeneous nature of postnatal NG2 cells. However, NG2 cells found in embryonic dates are far less understood. Our study indicates that early NG2 progenitors from a ventral origin (i.e., before embryonic day 16.5) tangentially migrate out of the medial ganglionic eminence and give rise to interneurons in deep layers of the dorsal cerebral cortex. The majority of myelinating oligodendrocytes found in both cortical gray and white matters are, in contrast, derived from NG2 progenitors with a neonatal subventricular zone origin. Our lineage tracing data reflect the heterogeneous nature of NG2 progenitor populations and define the relationship between lineage divergence and spatiotemporal origins. Beyond the typical lineage tracing studies of NG2 + cells, by costaining with lineage-specific markers, our study addresses the origins of heterogeneity and its implications in the differentiation potentials of NG2 + progenitors.lineage differentiation T he relationship between progenitor origins and their possible terminal cell fates in the central nervous system (CNS) development is a complex question that remains to be fully addressed. Depending on the origin from which a progenitor cell arises, physical and molecular regulatory mechanisms define both cell identity and direct specific lineage potentials during differentiation and migration. For example, cortical pyramidal neurons are generated in the ventricular zone (VZ) of the pallium and are guided by radial glia to their final position in the cortical plate (1, 2). However, cortical interneurons born in subpallium germinal zones during early embryonic dates tangentially migrate to the cortical plate up to the neonatal period. Not only neurons but also the differentiation of glial cells follow a specific spatial and temporal patterning (3, 4). The developmental origin of oligodendrocytes (OLs) is a longstanding controversial issue with many valid hypotheses (5). One hypothesis suggests that OLs are developed throughout all regions of the CNS, with multiple and diverse developmental origins that provide the progenitor sources of all OLs (6, 7). This hypothesis was challenged in the early 1990s as a series of observations suggested that commitment to the OL lineage occurs in a specialized domain of the ventral VZ in development of the spinal cord and forebrain (8). Both strategies provide mature OLs for myelination, but separate and distinct developmental regulatory strategies that direct the OL development are required for each scenario.The subpallium germinal zones are divided into three areas: the medial ganglionic eminence (MGE), the lateral ganglionic eminence, and the caudal ganglionic eminence. The distribution of cortical interneurons correlates with the origin of their progenitors (9, 10). Additional genetic studies have demonstrated that NG2 cells in the subpallium give rise to cortical interneurons (11)....

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“…Although NG2 cells remain proliferative throughout life, their cell cycle time lengthens significantly with age (Psachoulia et al, 2009; Young et al, 2013). However, it is noteworthy that significant clonal expansion of NG2 cells has been detected between P120 and P240 (Garcia-Marques, 2014). Similarly, the rate of oligodendrocyte differentiation and NG2 cell proliferation are greater in white matter than in gray matter (Young et al, 2013; Hill et al, 2013).…”

Section: Age-dependent Changes In Ng2 Cell Fatementioning

confidence: 99%

Lineage, fate, and fate potential of NG2-glia

et al. 2016

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NG2 cells represent a fourth major glial cell population in the mammalian central nervous system (CNS). They arise from discrete germinal zones in mid-gestation embryos and expand to occupy the entire CNS parenchyma. Genetic fate mapping studies have shown that oligodendrocytes and a subpopulation of ventral protoplasmic astrocytes arise from NG2 cells. This review describes recent findings on the fate and fate potential of NG2 cells under physiological and pathological conditions. We discuss age-dependent changes in the fate and fate potential of NG2 cells and possible mechanisms that could be involved in restricting their oligodendrocyte differentiation or fate plasticity.

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NG2-Glia from Pallial Progenitors Produce the Largest Clonal Clusters of the Brain: Time Frame of Clonal Generation in Cortex and Olfactory Bulb

Cited by 37 publications

References 52 publications

ASCL1 regulates proliferation of NG2‐glia in the embryonic and adult spinal cord

ASCL1 regulates proliferation of NG2‐glia in the embryonic and adult spinal cord

Spatiotemporally different origins of NG2 progenitors produce cortical interneurons versus glia in the mammalian forebrain

Lineage, fate, and fate potential of NG2-glia

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