Multiple Dorsoventral Origins of Oligodendrocyte Generation in the Spinal Cord and Hindbrain

Vallstedt, Anna; Klos, Joanna M.; Ericson, Johan

doi:10.1016/j.neuron.2004.12.026

Cited by 303 publications

(295 citation statements)

References 237 publications

(357 reference statements)

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“…In the spinal cord and hindbrain, the dorsal progenitors for oligodendrocytes emerge subsequent to a more abundant population of ventral progenitors and they appear to play a relatively minor role in total oligodendrogenesis there (Cai et al, 2005;Fogarty et al, 2005;Vallstedt et al, 2005). By analogy, dorsal progenitors might not play a major role in cortical oligodendrogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Much of the controversy regarding the origins of oligodendrocytes in the spinal cord and hindbrain has been recently resolved with the discovery of a late-arising pool of dorsal progenitors that contribute to a larger population of oligodendrocytes derived from progenitors in the ventral neural tube (Cai et al, 2005;Fogarty et al, 2005;Miller, 2005;Vallstedt et al, 2005). However, the relative contribution of dorsal and ventral progenitor cells to oligodendrocyte myelination in the cortex is highly contended in the brain development field (Spassky et al, 2000;Woodruff et al, 2001;Marshall et al, 2003;Miller, 2005).…”

Section: Introductionmentioning

confidence: 99%

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A Critical Role for Dorsal Progenitors in Cortical Myelination

et al. 2006

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Much controversy regarding the anatomical sources of oligodendrocytes in the spinal cord and hindbrain has been resolved. However, the relative contribution of dorsal and ventral progenitors to myelination of the cortex is still a subject of debate. To assess the contribution of dorsal progenitors to cortical myelination, we ablated the basic helix-loop-helix transcription factor Olig2 in the developing dorsal telencephalon. In Olig2-ablated cortices, myelination is arrested at the progenitor stage. Under these conditions, ventrally derived oligodendrocytes migrate dorsally into the Olig2-ablated territory but cannot fully compensate for myelination deficits observed at postnatal stages. Thus, spatially restricted ablation of Olig2 function unmasks a contribution of dorsal progenitors to cortical myelination that is much greater than hitherto appreciated.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Critical Role for Dorsal Progenitors in Cortical Myelination

et al. 2006

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“…Olig2 expression begins in the newly formed neural tube in response to both Shh and RA signals, and acts downstream of the class II proteins Nkx6.1 and Nkx6.2 (Lu et al 2000;Novitch et al 2001b;Novitch et al 2003;Cai et al 2005;Vallstedt et al 2005). After its induction, Olig2 participates in the dorsoventral pattering of progenitors through its ability to repress the class I protein Irx3 from the ventral neural tube (Mizuguchi et al 2001;Novitch et al 2001).…”

Section: Coordination Of Cell Fate and Neurogenic Differentiationmentioning

confidence: 99%

Regulatory pathways linking progenitor patterning, cell fates and neurogenesis in the ventral neural tube

Briscoe¹,

Novitch

2007

Phil. Trans. R. Soc. B

136

137

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The assembly of neural circuits in the vertebrate central nervous system depends on the organized generation of specific neuronal subtypes. Studies over recent years have begun to reveal the principles and elucidate some of the detailed mechanisms that underlie these processes. In general, exposure to different types and concentrations of signals directs neural progenitor populations to generate specific subtypes of neurons. These signals function by regulating the expression of intrinsic determinants, notably transcription factors, which specify the fate of cells as they differentiate into neurons. In this review, we illustrate these concepts by focusing on the generation of neurons in ventral regions of the spinal cord, where detailed knowledge of the mechanisms that regulate cell identity has provided insight into the development of a number of neuronal subtypes, including motor neurons. A greater knowledge of the molecular control of neural development is likely to have practical benefits in understanding the causes and consequences of neurological diseases. Moreover, recent studies have demonstrated how an understanding of normal neural development can be applied to direct differentiation of stem cells in vitro to specific neuronal subtypes. This type of rational manipulation of stem cells may represent the first step in the development of treatments based on therapeutic replacement of diseased or damaged nervous tissue.

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“…At later stages, a dorsal origin of oligodendrocytes has recently been reported in the fetus (26)(27)(28)(29). To determine whether dorsal or ventral spinal NG2 cell development requires Olig function during the embryonic and͞or fetal phases, we first investigated Olig2 Ϫ/Ϫ mutant spinal cord at 18.5 dpc.…”

Section: Olig Function Is Required For Early Ng2 Cell Development In Thementioning

confidence: 99%

Development of NG2 neural progenitor cells requires Olig gene function

Ligon

Kesari

Kitada³

et al. 2006

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

191

152

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In the adult central nervous system, two distinct populations of glial cells expressing the chondroitin sulfate proteoglycan NG2 have been described: bipolar progenitor cells and more differentiated ''synantocytes.'' These cells have diverse neurological functions, including critical roles in synaptic transmission, repair, and regeneration. Despite their potential importance, the genetic factors that regulate NG2 cell development are poorly understood, and the relationship of synantocytes to the oligodendroglial lineage, in particular, remains controversial. Here, we show that >90% of embryonic and adult NG2 cells express Olig2, a basic helix-loop-helix transcription factor required for oligodendrocyte lineage specification. Analysis of mice lacking Olig function demonstrates a failure of NG2 cell development at embryonic and perinatal stages that can be rescued by addition of a transgene containing the human OLIG2 locus. These findings show a general requirement for Olig function in NG2 cell development and highlight further roles for Olig transcription factors in neural progenitor cells.Cspg4 ͉ oligodendrocyte ͉ synantocyte ͉ glia ͉ regeneration N G2 cells are central nervous system (CNS) glial cells defined by their expression of the chondroitin sulfate proteoglycan, NG2, which is also known as Cspg4 or AN2 (1-4). A significant proportion of NG2 cells actively proliferate and indeed have been characterized as the most prevalent cycling progenitor cell population in the adult CNS (5, 6). NG2 cells have diverse functions and participate in oligodendrogenesis (7) and neurogenesis (8), as well as the physiologic support of neurons and synaptic signaling (4, 9). They have also been proposed to play critical roles in brain repair and regeneration and are the primary responding neural cell type to CNS injury (10, 11).Despite their abundance as a progenitor population and potential importance in maintenance and repair of neurological function, the developmental ontogeny of NG2 cells remains controversial (4,7,12). Cytologically, they are reportedly a heterogeneous population, and two distinctive cellular morphologies have been described: bipolar progenitor cells that resemble oligodendrocyte progenitors (OLP) (1, 13) and stellate ''synantocytes.'' Most postnatal NG2 cells are synantocytes, which are defined by a complex ''differentiated'' morphologic appearance. Even so, they lack expression of most differentiated glial celltype specific markers (12). Indeed, based on these observations, several studies have suggested that the majority of postnatal NG2ϩ synantocytes comprise an independent neuroepithelial lineage distinct from neurons, astrocytes, and oligodendrocytes (4, 12, 14), a proposal that has provoked ongoing debate (15, 16).The genetic pathways, which regulate NG2 cell development, have yet to be defined, and the question of whether bipolar NG2 cells and synantocytes have fundamentally similar or different origins is unresolved. Given their early developmental expression of OLP markers, NG2 cell formation mi...

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Multiple Dorsoventral Origins of Oligodendrocyte Generation in the Spinal Cord and Hindbrain

Cited by 303 publications

References 237 publications

A Critical Role for Dorsal Progenitors in Cortical Myelination

A Critical Role for Dorsal Progenitors in Cortical Myelination

Regulatory pathways linking progenitor patterning, cell fates and neurogenesis in the ventral neural tube

Development of NG2 neural progenitor cells requires Olig gene function

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