Frizzled 8a function is required for oligodendrocyte development in the zebrafish spinal cord

Kim, Suhyun; Kim, Seok Hyung; Kim, Ho; Chung, Ah Young; Yong, I.; Kim, Cheol-Hee; Huh, Tae Lin; Park, Hae Chul

doi:10.1002/dvdy.21739

Cited by 23 publications

(19 citation statements)

References 44 publications

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“…Activation of b-catenin inhibited developmental myelination and remyelination in rodents, and we show that the activated b-catenin/Tcf4 complex can act as an inhibitor of OLP differentiation in the mammalian CNS, a conclusion supported by recent investigation of frz8 function in zebrafish (Kim et al 2008). Furthermore, APC Min animals, which lack one copy of the catenin antagonist APC, also exhibited impaired remyelination, indicating that Wnt pathway regulation is critical for timely myelination and remyelination.…”

Section: Canonical Wnt Pathway Activation and Dysregulation Profoundlsupporting

confidence: 77%

“…Because we found reduced numbers of Olig2 cells (Fig. 5C), which labels OLPs and mature oligodendrocytes, and cell death is associated with wnt pathway activation in zebrafish neural tube (Kim et al 2008), we performed analysis of Caspase-3 expression. As shown in Supplemental Figure 3, the reduction in mature oligodendrocytes at P9 and P15 in the Olig2cre/DA-Cat cord (Fig.…”

Section: à5mentioning

confidence: 99%

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Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS

Fancy¹,

Baranzini²,

Zhao³

et al. 2009

Genes Dev.

558

634

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The progressive loss of CNS myelin in patients with multiple sclerosis (MS) has been proposed to result from the combined effects of damage to oligodendrocytes and failure of remyelination. A common feature of demyelinated lesions is the presence of oligodendrocyte precursors (OLPs) blocked at a premyelinating stage. However, the mechanistic basis for inhibition of myelin repair is incompletely understood. To identify novel regulators of OLP differentiation, potentially dysregulated during repair, we performed a genome-wide screen of 1040 transcription factor-encoding genes expressed in remyelinating rodent lesions. We report that ;50 transcription factor-encoding genes show dynamic expression during repair and that expression of the Wnt pathway mediator Tcf4 (aka Tcf7l2) within OLPs is specific to lesioned-but not normal-adult white matter. We report that b-catenin signaling is active during oligodendrocyte development and remyelination in vivo. Moreover, we observed similar regulation of Tcf4 in the developing human CNS and lesions of MS. Data mining revealed elevated levels of Wnt pathway mRNA transcripts and proteins within MS lesions, indicating activation of the pathway in this pathological context. We show that dysregulation of Wnt-b-catenin signaling in OLPs results in profound delay of both developmental myelination and remyelination, based on (1) conditional activation of b-catenin in the oligodendrocyte lineage in vivo and (2) findings from APC Min mice, which lack one functional copy of the endogenous Wnt pathway inhibitor APC. Together, our findings indicate that dysregulated Wnt-b-catenin signaling inhibits myelination/remyelination in the mammalian CNS. Evidence of Wnt pathway activity in human MS lesions suggests that its dysregulation might contribute to inefficient myelin repair in human neurological disorders.[Keywords: Oligodendrocyte; CNS development; Wnt; multiple sclerosis; remyelination; Olig2] Supplemental material is available at http://www.genesdev.org.

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Section: Canonical Wnt Pathway Activation and Dysregulation Profoundlsupporting

confidence: 77%

Section: à5mentioning

confidence: 99%

Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS

Fancy¹,

Baranzini²,

Zhao³

et al. 2009

Genes Dev.

558

634

View full text Add to dashboard Cite

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“…It has been previously shown that Wnt signaling delays oligodendrocyte differentiation (Kim et al, 2008;Fancy et al, 2009). We thus examined whether heat shocking ⌬TCF3 embryos resulted in defective myelin gene expression because of altered oligodendrocyte development.…”

Section: Interaction Between ␤-Catenin and Tcf3 Is Required For The Fmentioning

confidence: 99%

Wnt/β-Catenin Signaling Is an Essential and Direct Driver of Myelin Gene Expression and Myelinogenesis

Tawk¹,

Makoukji²,

Belle³

et al. 2011

J. Neurosci.

166

134

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“…5F). All of these receptors genes have been identified in the developing CNS and some have identified roles in NPC regulation [25][26][27][28]. As such, these receptors may provide specific means to target human multipotent NPCs.…”

Section: Cd140amentioning

confidence: 99%

CD133/CD140a-Based Isolation of Distinct Human Multipotent Neural Progenitor Cells and Oligodendrocyte Progenitor Cells

Wang

O’Bara²,

Pol³

et al. 2013

Stem Cells and Development

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The mechanisms underlying the specification of oligodendrocyte fate from multipotent neural progenitor cells (NPCs) in developing human brain are unknown. In this study, we sought to identify antigens sufficient to distinguish NPCs free from oligodendrocyte progenitor cells (OPCs). We investigated the potential overlap of NPC and OPC antigens using multicolor fluorescence-activated cell sorting (FACS) for CD133/PROM1, A2B5, and CD140a/PDGFaR antigens. Surprisingly, we found that CD133, but not A2B5, was capable of enriching for OLIG2 expression, Sox10 enhancer activity, and oligodendrocyte potential. As a subpopulation of CD133-positive cells expressed CD140a, we asked whether CD133 enriched bone fide NPCs regardless of CD140a expression. We found that CD133+ CD140a -cells were highly enriched for neurosphere initiating cells and were multipotent. Importantly, when analyzed immediately following isolation, CD133 + CD140a -NPCs lacked the capacity to generate oligodendrocytes. In contrast, CD133+ CD140a + cells were OLIG2-expressing OPCs capable of oligodendrocyte differentiation, but formed neurospheres with lower efficiency and were largely restricted to glial fate. Gene expression analysis further confirmed the stem cell nature of CD133 + CD140a -cells. As human CD133 + cells comprised both NPCs and OPCs, CD133 expression alone cannot be considered a specific marker of the stem cell phenotype, but rather comprises a heterogeneous mix of glial restricted as well as multipotent neural precursors. In contrast, CD133/CD140a-based FACS permits the separation of defined progenitor populations and the study of neural stem and oligodendrocyte fate specification in the human brain.

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Frizzled 8a function is required for oligodendrocyte development in the zebrafish spinal cord

Cited by 23 publications

References 44 publications

Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS

Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS

Wnt/β-Catenin Signaling Is an Essential and Direct Driver of Myelin Gene Expression and Myelinogenesis

CD133/CD140a-Based Isolation of Distinct Human Multipotent Neural Progenitor Cells and Oligodendrocyte Progenitor Cells

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