The Transcription Factor Yin Yang 1 Is Essential for Oligodendrocyte Progenitor Differentiation

He, Ye; Dupree, Jeff; Wang, Ju; Sandoval, Juan; Li, Jiadong; Liu, Huifei; Shi, Yang; Nave, Klaus Armin; Casaccia‐Bonnefil, Patrizia

doi:10.1016/j.neuron.2007.06.029

Cited by 240 publications

(279 citation statements)

References 88 publications

(79 reference statements)

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“…It is possible that changes to the size and structure of the nucleus induce transcriptional activity necessary for oligodendrocyte differentiation. Perhaps an increase in cell density affects transcription factors known to regulate differentiation, such as Nkx2.2, Sox10, Olig2, and the recently identified Yin Yang 1 (14)(15)(16)(17). Understanding the relationship between intrinsic and extrinsic factors could help identify environmental conditions that will promote oligodendrocyte differentiation in the presence of chronic demyelination.…”

Section: Discussionmentioning

confidence: 99%

The geometric and spatial constraints of the microenvironment induce oligodendrocyte differentiation

Rosenberg

Kelland

Tokar

et al. 2008

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

189

188

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The oligodendrocyte precursor cell (OPC) arises from the subventricular zone (SVZ) during early vertebrate development to migrate and proliferate along axon tracts before differentiating into the myelin-forming oligodendrocyte. We demonstrate that the spatial and temporal regulation of oligodendrocyte differentiation depends intimately on the axonal microenvironment and the density of precursor cells along a specified axonal area. Differentiation does not require dynamic axonal signaling, but instead is induced by packing constraints resulting from intercellular interactions. Schwann cells and even artificial beads bound to the axonal surface can mimic these constraints and promote differentiation. Together, these results describe the coordinately controlled biophysical interaction of oligodendrocyte precursors within an axonal niche leading to self-renewal and differentiation.myelination ͉ neuronal-glial interactions ͉ mechanotransduction D amage to the myelin membrane, as a result of nerve injury or disease, significantly impairs the ability of the nervous system to communicate and can lead to a host of debilitating symptoms, as well as an ultimate loss of function. In the CNS, demyelination is accompanied by the loss of oligodendrocytes, the terminally differentiated cells responsible for the formation of the myelin sheath. After the initial onset of demyelination, OPCs are induced to differentiate and remyelinate, effectively replacing lost oligodendrocytes. Unfortunately, the capacity for remyelination is limited, and ultimately fails in the presence of chronic demyelination. It remains unclear why the CNS cannot sustain this initial ability to repair the myelin sheath. One possible explanation is that adult OPCs eventually lose their ability to differentiate into remyelinating oligodendrocytes (1). It is plausible that the continuous presence of a demyelinating environment is responsible for inhibiting the differentiation process. If this supposition is true, then it is imperative to identify the environmental conditions conducive to the ongoing production of oligodendrocytes.Examining oligodendrocyte generation during development could prove useful for determining the role of the environment in the induction of differentiation. Developing OPCs are proliferative and self-renewing cells that originate in the SVZ and migrate along axons throughout the CNS. During development, an OPC must decide how many times it will divide, and where it will migrate. Also, an OPC must choose whether to remain as a precursor cell into adulthood or to differentiate into a myelinating oligodendrocyte. Such complex decisions are likely to be heavily influenced by the nature of the surrounding environment and by the behavior of neighboring cells. Based on these assumptions, it is our goal to identify the environmental factors that influence the decision of an OPC to differentiate into an oligodendrocyte. To accomplish this goal, we first looked at the developing rat spinal cord to examine the temporal regulation of oligodendrocy...

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Section: Discussionmentioning

confidence: 99%

The geometric and spatial constraints of the microenvironment induce oligodendrocyte differentiation

Rosenberg

Kelland

Tokar

et al. 2008

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

189

188

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“…The initial specification of the oligodendrocyte lineage is dependent on olig2 and this lineage is absent from olig2-null mice [17] . olig2 induces transcription factors that are required for the generation of mature, postmitotic oligodendrocytes, notably olig1, Sox-10, Nkx2.2, Nkx6.2, Ying Yang 1, and ZFP488 [18][19][20][21][22][23] . in counterbalance, transcription [24][25][26] .…”

Section: Intrinsic Signalsmentioning

confidence: 99%

Promoting remyelination for the treatment of multiple sclerosis: opportunities and challenges

Zhang

Guo

2013

Neurosci. Bull.

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Multiple sclerosis (MS) is a chronic and devastating autoimmune demyelinating disease of the central nervous system. With the increased understanding of the pathophysiology of this disease in the past two decades, many disease-modifying therapies that primarily target adaptive immunity have been shown to prevent exacerbations and new lesions in patients with relapsing-remitting MS. However, these therapies only have limited efficacy on the progression of disability. Increasing evidence has pointed to innate immunity, axonal damage and neuronal loss as important contributors to disease progression. Remyelination of denuded axons is considered an effective way to protect neurons from damage and to restore neuronal function. The identification of several key molecules and pathways controlling the differentiation of oligodendrocyte progenitor cells and myelination has yielded clues for the development of drug candidates that directly target remyelination and neuroprotection. The long-term efficacy of this strategy remains to be evaluated in clinical trials. Here, we provide an overview of current and emerging therapeutic concepts, with a focus on the opportunities and challenges for the remyelination approach to the treatment of MS.

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“…S6B). In addition, promoter region reporter assays revealed that two important oligodendrocyte-associated transcription factors for OPCs differentiation to OLs, YY1 and Nkx2.2 (17,18), display positive effects on the expression of 2700046G09Rik (Fig. 5G).…”

Section: Overexpression Of Mir-23a Leads To Enhanced Myelination In Thementioning

confidence: 99%

MicroRNA-23a promotes myelination in the central nervous system

Lin¹,

Huang

Zhang³

et al. 2013

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

110

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Demyelinating disorders including leukodystrophies are devastating conditions that are still in need of better understanding, and both oligodendrocyte differentiation and myelin synthesis pathways are potential avenues for developing treatment. Overexpression of lamin B1 leads to leukodystrophy characterized by demyelination of the central nervous system, and microRNA-23 (miR-23) was found to suppress lamin B1 and enhance oligodendrocyte differentiation in vitro. Here, we demonstrated that miR23a-overexpressing mice have increased myelin thickness, providing in vivo evidence that miR-23a enhances both oligodendrocyte differentiation and myelin synthesis. Using this mouse model, we explored possible miR-23a targets and revealed that the phosphatase and tensin homologue/phosphatidylinositol trisphosphate kinase/Akt/mammalian target of rapamycin pathway is modulated by miR-23a. Additionally, a long noncoding RNA, 2700046G09Rik, was identified as a miR-23a target and modulates phosphatase and tensin homologue itself in a miR-23a-dependent manner. The data presented here imply a unique role for miR-23a in the coordination of proteins and noncoding RNAs in generating and maintaining healthy myelin.M icroRNAs (miRNAs) play an important role in regulating a large number of developmental processes and diseases (1-3) through fine tuning biological networks (4, 5). Expression levels of miRNAs in oligodendroglia vary according to their differentiation stages, indicating a possible role for miRNAs in regulating developmental processes among migratory, proliferating, and myelinating oligodendrocytes (OLs) (6-9). Disruption of miRNA biogenesis by Dicer ablation in oligodendroglia at postdevelopmental stages results in a neurodegenerative phenotype including demyelination, inflammation, and axon loss (10), suggesting that miRNAs are also important for myelin maintenance at later developmental stages. miR-23 is among the most abundant miRNAs in OLs (6, 7). Previously, we reported that in the presence of excess miR-23 in vitro, a greater proportion of cells express mature markers of OLs that are paralleled by multipolar morphological appearance with increased levels of mature myelin proteins, indicating that miR-23 can enhance oligodendrogenesis (11). In contrast, excessive lamin B1, a nuclear envelope protein and target of miR-23, leads to lower numbers of cells expressing mature markers with reduced levels of mature myelin proteins both in vitro and in vivo, suggesting defective differentiation of OLs. Importantly, the adverse effects of lamin B1 on OL cells can be abrogated by overexpressing miR-23, which functions as a negative regulator of lamin B1.Here, we use mice in which miR-23a (one of the two miR-23 isoforms: miR-23a and b) overexpression is driven by an OLspecific promoter [2′,3′-cyclic nucleotide 3′-phophodiesterase (Cnp)] to investigate the effects of miR-23a on OL differentiation and myelin synthesis in vivo. We demonstrated that in addition to the previously identified target, lamin B1, miR-23a also directly modul...

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The Transcription Factor Yin Yang 1 Is Essential for Oligodendrocyte Progenitor Differentiation

Cited by 240 publications

References 88 publications

The geometric and spatial constraints of the microenvironment induce oligodendrocyte differentiation

The geometric and spatial constraints of the microenvironment induce oligodendrocyte differentiation

Promoting remyelination for the treatment of multiple sclerosis: opportunities and challenges

MicroRNA-23a promotes myelination in the central nervous system

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