Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Ascl1/Mash1 promotes brain oligodendrogenesis during myelination and remyelination.
Nakatani H
,
Martin E
,
Hassani H
,
Clavairoly A
,
Maire CL
,
Viadieu A
,
Kerninon C
,
Delmasure A
,
Frah M
,
Weber M
,
Nakafuku M
,
Zalc B
,
Thomas JL
,
Guillemot F
,
Nait-Oumesmar B
,
Parras C
.
???displayArticle.abstract???
Oligodendrocytes are the myelin-forming cells of the CNS. They differentiate from oligodendrocyte precursor cells (OPCs) that are produced from progenitors throughout life but more actively during the neonatal period and in response to demyelinating insults. An accurate regulation of oligodendrogenesis is required to generate oligodendrocytes during these developmental or repair processes. We hypothesized that this regulation implicates transcription factors, which are expressed by OPCs and/or their progenitors. Ascl1/Mash1 is a proneural transcription factor previously implicated in embryonic oligodendrogenesis and operating in genetic interaction with Olig2, an essential transcriptional regulator in oligodendrocyte development. Herein, we have investigated the contribution of Ascl1 to oligodendrocyte development and remyelination in the postnatal cortex. During the neonatal period, Ascl1 expression was detected in progenitors of the cortical subventricular zone and in cortical OPCs. Different genetic approaches to delete Ascl1 in cortical progenitors or OPCs reduced neonatal oligodendrogenesis, showing that Ascl1 positively regulated both OPC specification from subventricular zone progenitors as well as the balance between OPC differentiation and proliferation. Examination of remyelination processes, both in the mouse model for focal demyelination of the corpus callosum and in multiple sclerosis lesions in humans, indicated that Ascl1 activity was upregulated along with increased oligodendrogenesis observed in remyelinating lesions. Additional genetic evidence indicated that remyelinating oligodendrocytes derived from Ascl1(+) progenitors/OPCs and that Ascl1 was required for proper remyelination. Together, our results show that Ascl1 function modulates multiple steps of OPC development in the postnatal brain and in response to demyelinating insults.
Aguirre,
A functional role for EGFR signaling in myelination and remyelination.
2007, Pubmed
Aguirre,
A functional role for EGFR signaling in myelination and remyelination.
2007,
Pubmed
Arnett,
bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS.
2004,
Pubmed
Bertrand,
Proneural genes and the specification of neural cell types.
2002,
Pubmed
Bhat,
Expression of the APC tumor suppressor protein in oligodendroglia.
1996,
Pubmed
Boda,
The GPR17 receptor in NG2 expressing cells: focus on in vivo cell maturation and participation in acute trauma and chronic damage.
2011,
Pubmed
Boutin,
Efficient in vivo electroporation of the postnatal rodent forebrain.
2008,
Pubmed
Cai,
Co-localization of Nkx6.2 and Nkx2.2 homeodomain proteins in differentiated myelinating oligodendrocytes.
2010,
Pubmed
Casarosa,
Mash1 regulates neurogenesis in the ventral telencephalon.
1999,
Pubmed
Castro,
A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets.
2011,
Pubmed
Chen,
The oligodendrocyte-specific G protein-coupled receptor GPR17 is a cell-intrinsic timer of myelination.
2009,
Pubmed
Fancy,
Increased expression of Nkx2.2 and Olig2 identifies reactive oligodendrocyte progenitor cells responding to demyelination in the adult CNS.
2004,
Pubmed
Fancy,
Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS.
2009,
Pubmed
Franklin,
Remyelination in the CNS: from biology to therapy.
2008,
Pubmed
Gokhan,
Combinatorial profiles of oligodendrocyte-selective classes of transcriptional regulators differentially modulate myelin basic protein gene expression.
2005,
Pubmed
Gorski,
Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage.
2002,
Pubmed
Hack,
Regionalization and fate specification in neurospheres: the role of Olig2 and Pax6.
2004,
Pubmed
Hall,
Spinal cord oligodendrocytes develop from ventrally derived progenitor cells that express PDGF alpha-receptors.
1996,
Pubmed
Ivanova,
Evidence for a second wave of oligodendrogenesis in the postnatal cerebral cortex of the mouse.
2003,
Pubmed
Kessaris,
Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage.
2006,
Pubmed
Kitada,
Transcription factor co-expression patterns indicate heterogeneity of oligodendroglial subpopulations in adult spinal cord.
2006,
Pubmed
Kondo,
Basic helix-loop-helix proteins and the timing of oligodendrocyte differentiation.
2000,
Pubmed
Lassmann,
Neuropathology in multiple sclerosis: new concepts.
1998,
Pubmed
Li,
Phosphorylation regulates OLIG2 cofactor choice and the motor neuron-oligodendrocyte fate switch.
2011,
Pubmed
Ligon,
Olig gene function in CNS development and disease.
2006,
Pubmed
Liu,
Induction of oligodendrocyte differentiation by Olig2 and Sox10: evidence for reciprocal interactions and dosage-dependent mechanisms.
2007,
Pubmed
Lu,
Ectopic expression of Olig1 promotes oligodendrocyte formation and reduces neuronal survival in developing mouse cortex.
2001,
Pubmed
Menn,
Origin of oligodendrocytes in the subventricular zone of the adult brain.
2006,
Pubmed
Miguez,
Opposing roles for Hoxa2 and Hoxb2 in hindbrain oligodendrocyte patterning.
2012,
Pubmed
,
Xenbase
Mizuguchi,
Combinatorial roles of olig2 and neurogenin2 in the coordinated induction of pan-neuronal and subtype-specific properties of motoneurons.
2001,
Pubmed
Nait-Oumesmar,
Activation of the subventricular zone in multiple sclerosis: evidence for early glial progenitors.
2007,
Pubmed
Nait-Oumesmar,
Progenitor cells of the adult mouse subventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination.
1999,
Pubmed
Nait-Oumesmar,
The role of SVZ-derived neural precursors in demyelinating diseases: from animal models to multiple sclerosis.
2008,
Pubmed
Pacary,
Proneural transcription factors regulate different steps of cortical neuron migration through Rnd-mediated inhibition of RhoA signaling.
2011,
Pubmed
Parras,
Mash1 specifies neurons and oligodendrocytes in the postnatal brain.
2004,
Pubmed
Parras,
The proneural gene Mash1 specifies an early population of telencephalic oligodendrocytes.
2007,
Pubmed
Petryniak,
Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain.
2007,
Pubmed
Qi,
Control of oligodendrocyte differentiation by the Nkx2.2 homeodomain transcription factor.
2001,
Pubmed
Rivers,
PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice.
2008,
Pubmed
Scott,
SOX9 induces and maintains neural stem cells.
2010,
Pubmed
Soriano,
Generalized lacZ expression with the ROSA26 Cre reporter strain.
1999,
Pubmed
Spassky,
Multiple restricted origin of oligodendrocytes.
1998,
Pubmed
Srinivas,
Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus.
2001,
Pubmed
Staugaitis,
NG2-positive glia in the human central nervous system.
2009,
Pubmed
Stolt,
The Sox9 transcription factor determines glial fate choice in the developing spinal cord.
2003,
Pubmed
Stolt,
Transcription factors Sox8 and Sox10 perform non-equivalent roles during oligodendrocyte development despite functional redundancy.
2004,
Pubmed
Sugiarto,
Asymmetry-defective oligodendrocyte progenitors are glioma precursors.
2011,
Pubmed
Sugimori,
Combinatorial actions of patterning and HLH transcription factors in the spatiotemporal control of neurogenesis and gliogenesis in the developing spinal cord.
2007,
Pubmed
Sun,
Olig bHLH proteins interact with homeodomain proteins to regulate cell fate acquisition in progenitors of the ventral neural tube.
2001,
Pubmed
Tekki-Kessaris,
Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon.
2001,
Pubmed
Vierbuchen,
Direct conversion of fibroblasts to functional neurons by defined factors.
2010,
Pubmed
Vierbuchen,
Molecular roadblocks for cellular reprogramming.
2012,
Pubmed
,
Xenbase
Waclaw,
Distinct temporal requirements for the homeobox gene Gsx2 in specifying striatal and olfactory bulb neuronal fates.
2009,
Pubmed
Wang,
A role for the helix-loop-helix protein Id2 in the control of oligodendrocyte development.
2001,
Pubmed
Watanabe,
Transient upregulation of Nkx2.2 expression in oligodendrocyte lineage cells during remyelination.
2004,
Pubmed
Yue,
A critical role for dorsal progenitors in cortical myelination.
2006,
Pubmed
Yun,
Id4 regulates neural progenitor proliferation and differentiation in vivo.
2004,
Pubmed
Zhou,
The bHLH transcription factor Olig2 promotes oligodendrocyte differentiation in collaboration with Nkx2.2.
2001,
Pubmed
Zhou,
The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification.
2002,
Pubmed
Zhu,
Age-dependent fate and lineage restriction of single NG2 cells.
2011,
Pubmed
Zhu,
Olig2-dependent developmental fate switch of NG2 cells.
2012,
Pubmed
