Wnt signaling regulates the sequential onset of neurogenesis and gliogenesis via induction of BMPs

Kasai, Mana; Satoh, Kiyoshi; Akiyama, Tetsu

doi:10.1111/j.1365-2443.2005.00876.x

Cited by 76 publications

(71 citation statements)

References 35 publications

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“…In the developing spinal cord and telencephalon, Wnt signaling controls the timing of oligodendrocyte maturation by inhibiting progenitors in an immature state, without changing proliferation of precursors [95][96][97]. In contrast, Wnt signaling promotes neural differentiation, presumably to prevent oligodendrocyte maturation before axons are appropriate for myelination [98]. In agreement with this, SOX17, one of the identified transcription factors that regulate OPC cell cycle exit and differentiation, directly antagonizes β-catenin [99].…”

Section: Wnt Signalingsupporting

confidence: 53%

Remyelination Therapy for Multiple Sclerosis

Keough

Yong

2013

Neurotherapeutics

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Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by infiltration of immune cells and progressive damage to myelin and axons. All therapeutics used to treat MS have been developed to target an overactive immune response, with aims to reduce disease activity. Chronic demyelinated axons are further prone to irreversible damage and death, and it is imperative that new therapies address this critical issue. Remyelination, the generation of new myelin in the adult nervous system, is an endogenous repair mechanism that restores function of denuded axons and delays their deterioration. Although remyelination can be extensive in some patients, the majority of cases limit repair only to the acute phase of disease. A significant current drive in new MS therapeutics is to identify targets that can promote remyelination by boosting endogenous oligodendrocyte precursor cells to form new myelin. Also, a number of inhibitory pathways have been identified in chronic MS lesions that prevent oligodendrocyte precursor cells from being properly recruited to demyelinated lesions or interfere with their differentiation to myelin-forming oligodendrocytes. In this review, we introduce the phenomenon of remyelination from the view of experimental models and studies in MS patients, describe a potential role in remyelination for currently available MS mediations, and discuss many avenues that are being actively studied to promote remyelination. The next frontier in MS therapeutics will supplement immunomodulation with agents that directly foster myelin repair, with aims to delay disease progression and recover lost neurological functions.

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Section: Wnt Signalingsupporting

confidence: 53%

Remyelination Therapy for Multiple Sclerosis

Keough

Yong

2013

Neurotherapeutics

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“…These receptors subsequently activate the JAK/STAT intracellular pathway, leading to the expression of GFAP in astrocytes (7)(8)(9). Most of the other pathways known to participate in GFAP expression are connected at some point to this canonical pathway (10,11). For example, some members of the tumor growth factor-␤ (TGF-␤) superfamily of cytokines have little or no effect on GFAP synthesis by themselves, but they strongly potentiate GFAP induced by the IL-6 family of cytokines.…”

Section: The Intermediate Filament Protein Glial Fibrillary Acidic Prmentioning

confidence: 99%

Synergistic Effect of Retinoic Acid and Cytokines on the Regulation of Glial Fibrillary Acidic Protein Expression

Herrera

Chen

Schubert

2010

Journal of Biological Chemistry

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Glial fibrillary acidic protein (GFAP) is the main astroglial marker during astrogliogenesis, but it is also expressed in other cell types, including neural stem cells and old neurons. Activation of the JAK/STAT pathway by the IL-6 family of cytokines is the canonical pathway regulating GFAP expression, whereas retinoic acid is thought to be the only inducer of GFAP to operate independently of this pathway. Here, we show that retinoic acid receptor ␣ not only links retinoic acid signaling to the canonical cytokine-stimulated pathway leading to GFAP expression but that it also plays a key role in the synergistic actions of retinoic acid and cytokines on this pathway. Cytokines both potentiate retinoic acid receptor ␣ expression and enhance its binding to DNA and to the Stat3-p300/CBP-Smad transcriptional complex, the cornerstone of the canonical pathway. PI3K is upstream to all the key events leading to the expression of GFAP. Our results give new insights about the role of retinoic acid signaling in GFAP expression.The intermediate filament protein glial fibrillary acidic protein (GFAP) 2 is considered a cell type-specific marker for astrocytes. However, GFAP is expressed in some nerve cell populations, including hippocampal neurons of older individuals (1). It is also expressed in some precursor populations of nerve cells as well as in cells that can give rise to both nerve and glia (2-4). Finally, the expression levels of GFAP within individual cells is extremely variable, and higher expression levels may limit the tumorigenicity of subpopulations of cells within glioblastomas (5, 6). Because of the wide range of cellular phenotypes associated with GFAP, it is important to understand the molecular mechanisms that regulate its expression.The GFAP is regulated in part by the secretion of factors into the extracellular space (7). The canonical pathway for GFAP expression in astrocytes is triggered by the binding of cytokines from the interleukin-6 (IL-6) family to their receptors. These receptors subsequently activate the JAK/STAT intracellular pathway, leading to the expression of GFAP in astrocytes (7-9). Most of the other pathways known to participate in GFAP expression are connected at some point to this canonical pathway (10, 11). For example, some members of the tumor growth factor-␤ (TGF-␤) superfamily of cytokines have little or no effect on GFAP synthesis by themselves, but they strongly potentiate GFAP induced by the IL-6 family of cytokines. They do so by triggering the phosphorylation, activation, and heterodimerization of Smad proteins, which then form a more potent transcriptional complex with p300/CBP and Stat3. As a consequence, the expression of GFAP is greatly enhanced (9, 12-14).All-trans-retinoic acid (RA), generally considered to be a neurogenic agent, is in fact a potent inducer of GFAP (14 -18). Studies with pharmacological agonists for the different retinoic acid receptors indicate that retinoic acid-induced GFAP expression is mediated by the activation of retinoic acid receptor (RAR) ␣ ...

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“…49 It seems that β-catenin, a centrol player of Wnt signaling, exerts effects on proliferation and differentiation or both, depending on the context of other signaling cascades. 12 The effects of Wnt signaling in cultured neural progenitor cells are modified from pro-differentiation to neuronal fate in an instructive manner. It induces neuronal differentiation through promoting proneural Ngn1 and Ngn2 expression 49 and suppressing Hes1 and Hes5 expression in late embryonic and postnatal development stages 14 (Fig.…”

Section: Regulatory Factors In Neuronal Fate Determinationmentioning

confidence: 99%

“…11 Many studies show that this signaling induces neuronal and astroglial differentiation but suppresses oligodendroglial differentiation. [11][12][13] Wnt signaling promotes proliferation of early NPCs, while plays positive roles in neurogenic phase, 14 presumably due to the difference of epigenetic statuses in the early and late NPCs.…”

Section: Major Signaling Pathways Involved In Cns Developmentmentioning

confidence: 99%

“…In addition to neuronal induction, Wnt signaling is able to promote astroglial differentiation and suppresses oligodendroglial differentiation in phase-dependent fashion through indirectly regulating gliogenesis by inducing BMPs in neuronal cells. 12,75 Wnt-induced BMPs are then secreted to the extracellular space to promote astroglial differentiation and inhibit oligodendroglial differentiation of surrounding cells. Oligodendroglial differentiation can only proceed when attenuation of Wnt and BMP signaling occurs.…”

Section: Regulatory Factors In Astroglial Fate Determinationmentioning

confidence: 99%

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Dynamic signaling for neural stem cell fate determination

Wen

Liu

2009

Cell Adhesion & Migration

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Central nervous system (CNS) development starts from neural stem cells (NSCs) which ultimately give rise to the three major cell types (neurons, oligodendrocytes and astrocytes) of the CNS. NSCs are specified in space-and time-related fashions, becoming spatially heterogeneous and generating a progressively restricted repertoire of cell types. Mammalian NSCs produce different cell types at different time points during development under the influence of multiple signaling pathways. These pathways act in a dynamic web mode to determine the fate of NSCs via modulating the expression and activity of distinct set of transcription factors which in turn trigger the transcription of neural fate-associated genes. This review thus introduces the major signal pathways, transcription factors and their cross-talks and coordinative interactions in NSC fate determination.

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Wnt signaling regulates the sequential onset of neurogenesis and gliogenesis via induction of BMPs

Cited by 76 publications

References 35 publications

Remyelination Therapy for Multiple Sclerosis

Remyelination Therapy for Multiple Sclerosis

Synergistic Effect of Retinoic Acid and Cytokines on the Regulation of Glial Fibrillary Acidic Protein Expression

Dynamic signaling for neural stem cell fate determination

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