Sonic Hedgehog Is Required during an Early Phase of Oligodendrocyte Development in Mammalian Brain

Alberta, John A.; Park, Song-Kyu; Mora, José O.; Yuk, Dongin; Pawlitzky, Inka; Iannarelli, Palma; Vartanian, Timothy; Stiles, Charles D.; Rowitch, David H.

doi:10.1006/mcne.2001.1026

Cited by 80 publications

(84 citation statements)

References 43 publications

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“…Additionally, three independent experiments were performed exposing 4 ϫ 10 6 dissociated ASA ϩ/ϩ and ASA Ϫ/Ϫ NPs to PDGF-AA ligand at a concentration of 20 ng/ml for 30 min before cell collection. For these experiments, NPs were starved for 3 h of growth factors present in the proliferating medium (EGF and basic FGF) and exposed to MG132 or NH 4 Cl as described above. After starvation, NP metabolism was slowed down by an ice bath for 15 min, cells were pelleted, and medium was preserved on ice.…”

Section: Methodsmentioning

confidence: 99%

“…Pelleted NPs were exposed to fresh medium containing PDGF-AA for 30 min on ice. Cells were pelleted and washed to remove unbound ligand and resuspended in their original medium with MG132 or NH 4 Cl for an additional 30 min at 37°C. NPs were pelleted, washed with PBS, and collected for Western blot analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Oligodendrocyte progenitor cells (OPCs) 2 are primarily generated from undifferentiated multipotential neural precursors (NPs) during early embryogenesis under the influence of morphogenic molecules, such as Shh (sonic hedgehog) (1)(2)(3)(4). Multiple mechanisms are developmentally coordinated to regulate the differentiation of OPCs into functional oligodendrocytes (OLs) (5)(6)(7).…”

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confidence: 99%

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Dysfunction of Platelet-derived Growth Factor Receptor α (PDGFRα) Represses the Production of Oligodendrocytes from Arylsulfatase A-deficient Multipotential Neural Precursor Cells

Pituch

Moyano

Lopez-Rosas

et al. 2015

Journal of Biological Chemistry

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Background: PDGFR␣ is a key signaling component in oligodendrogenesis. Results: Multipotential Neural precursors (NPs) deficient in arylsulfatase A (ASA) show a higher ratio of long versus short fatty acid sulfatides, reduction in PDGFR␣, decreased AKT phosphorylation, and increased exosomal shedding of PDGFR␣. Conclusion: Sulfatides are regulators of NP response to PDGF-AA. Significance: A novel regulatory mechanism of PDGFR␣ signaling is described.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Dysfunction of Platelet-derived Growth Factor Receptor α (PDGFRα) Represses the Production of Oligodendrocytes from Arylsulfatase A-deficient Multipotential Neural Precursor Cells

Pituch

Moyano

Lopez-Rosas

et al. 2015

Journal of Biological Chemistry

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“…106 Interestingly, MASH1 is expressed in oligodendrocyte progenitors and might have a role in specifying the differentiation of oligodendrocytes from immature glial cells. 107 Other oligodendrocyte-specifying TFs include bHLH proteins OLIG1 and OLIG2 that are activated by Shh 108 and bFGF signals. 109 OLIG2 regulates the development of oligodendrocytes by enabling the differentiation of NG2-positive synantocytes into the oligodendroglial lineage.…”

Section: Micrornamentioning

confidence: 99%

Transcription factors and neural stem cell self-renewal, growth and differentiation

Ahmed

Gan

Lam

et al. 2009

Cell Adhesion & Migration

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The central nervous system (CNS) is a large network of interconnecting and intercommunicating cells that form functional circuits. Disease and injury of the CNS are prominent features of the healthcare landscape. There is an urgent unmet need to generate therapeutic solutions for CNS disease/injury. To increase our understanding of the CNS we need to generate cellular models that are experimentally tractable. Neural stem cells (NSCs), cells that generate the CNS during embryonic development, have been identified and propagated in vitro. To develop NSCs as a cellular model for the CNS we need to understand more about their genetics and cell biology. In particular, we need to define the mechanisms of self-renewal, proliferation and differentiation-i.e. NSC behavior. The analysis of pluripotency of embryonic stem cells through mapping regulatory networks of transcription factors has proven to be a powerful approach to understanding embryonic development. Here, we discuss the role of transcription factors in NSC behavior.

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“…Oligodendrocyte specification occurs at late embryonic and early postnatal periods (Miller, 1996;Lee et al, 2000). Extracellular sonic hedgehog (Shh) signal in ventral telencephalon is necessary and sufficient for inducing commitment to oligodendrocyte precursors (Alberta et al, 2001;Tekki-Kessaris et al, 2001). Downstream to Shh signaling, two bHLH transcription factors, Olig1 and Olig2, are particularly important for oligodendrocyte development (Lu et al, 2001(Lu et al, , 2002Zhou et al, 2001;Zhou and Anderson, 2002).…”

Section: Introductionmentioning

confidence: 99%

A Critical Cell-Intrinsic Role for Serum Response Factor in Glial Specification in the CNS

Lu¹,

Ramanan²

2012

Journal of Neuroscience

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Astrocytes and oligodendrocytes play crucial roles in nearly every facet of nervous system development and function, including neuronal migration, synaptogenesis, synaptic plasticity, and myelination. Previous studies have widely characterized the signaling pathways important for astrocyte differentiation and unveiled a number of transcription factors that guide oligodendrocyte differentiation in the CNS. However, the identities of the transcription factors critical for astrocyte specification in the brain remain unknown. Here we show that deletion of the stimulus-dependent transcription factor, serum response factor (SRF), in neural precursor cells (NPCs) (Srf-NestincKO) results in nearly 60% loss in astrocytes and 50% loss in oligodendrocyte precursors at birth. Cultured SRF-deficient NPCs exhibited normal growth rate and capacity to self-renew. However, SRF-deficient NPCs generated fewer astrocytes and oligodendrocytes in response to several lineage-specific differentiation factors. These deficits in glial differentiation were rescued by ectopic expression of wild-type SRF in SRF-deficient NPCs. Interestingly, ectopic expression of a constitutively active SRF (SRF-VP16) in NPCs augmented astrocyte differentiation in the presence of pro-astrocytic factors. However, SRF-VP16 expression in NPCs had an inhibitory effect on oligodendrocyte differentiation. In contrast, mice carrying conditional deletion of SRF in developing forebrain neurons (Srf-NEX-cKO) did not exhibit any deficits in astrocytes in the brain. Together, our observations suggest that SRF plays a critical cell-autonomous role in NPCs to regulate astrocyte and oligodendrocyte specification in vivo and in vitro.

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Sonic Hedgehog Is Required during an Early Phase of Oligodendrocyte Development in Mammalian Brain

Cited by 80 publications

References 43 publications

Dysfunction of Platelet-derived Growth Factor Receptor α (PDGFRα) Represses the Production of Oligodendrocytes from Arylsulfatase A-deficient Multipotential Neural Precursor Cells

Dysfunction of Platelet-derived Growth Factor Receptor α (PDGFRα) Represses the Production of Oligodendrocytes from Arylsulfatase A-deficient Multipotential Neural Precursor Cells

Transcription factors and neural stem cell self-renewal, growth and differentiation

A Critical Cell-Intrinsic Role for Serum Response Factor in Glial Specification in the CNS

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