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- Title
Ascll/Mashl Promotes Brain Oligodendrogenesis during Myelination and Remyelination.
- Authors
Nakatani, Hiroko; Martin, Elodie; Hassani, Hessameh; Clavairoly, Adrien; Maire, Cécile L.; Viadieu, Arthur; Kerninon, Christophe; Delmasure, Aurèlie; Frah, Magali; Weber, Melanie; Nakafuku, Masato; Zalc, Bernard; Thomas, Jean-Léon; Guillemot, François; Nait-Oumesmar, Brahim; Parras, Carlos
- 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. Ascll/Mashl is a proneural transcription factor previously implicated in embryonic oligodendrogenesis and operating in genetic interaction with 01ig2, an essential transcriptional regulator in oligodendrocyte development. Herein, we have investigated the contribution of Ascii to oligodendro-cyte development and remyelination in the postnatal cortex. During the neonatal period, Ascii expression was detected in progenitors of the cortical subventricular zone and in cortical OPCs. Different genetic approaches to delete Ascii in cortical progenitors or OPCs reduced neonatal oligodendrogenesis, showing that Ascii 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 Ascii activity was upregulated along with increased oligodendro-genesis observed in remyelinating lesions. Additional genetic evidence indicated that remyelinating oligodendrocytes derived from Ascii ' progenitors/OPCs and that Ascii was required for proper remyelination. Together, our results show that Ascii function modulates multiple steps of OPC development in the postnatal brain and in response to demyelinating insults.
- Subjects
BRAIN physiology; OLIGODENDROGLIA; PROGENITOR cells; MYELINATION; CENTRAL nervous system; TRANSCRIPTION factors; CHEMICAL precursors
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 23, p9752
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0805-13.2013