TY - JOUR T1 - Ascl1/Mash1 Promotes Brain Oligodendrogenesis during Myelination and Remyelination JF - The Journal of Neuroscience JO - J. Neurosci. SP - 9752 LP - 9768 DO - 10.1523/JNEUROSCI.0805-13.2013 VL - 33 IS - 23 AU - Hiroko Nakatani AU - Elodie Martin AU - Hessameh Hassani AU - Adrien Clavairoly AU - Cécile L. Maire AU - Arthur Viadieu AU - Christophe Kerninon AU - Aurélie Delmasure AU - Magali Frah AU - Melanie Weber AU - Masato Nakafuku AU - Bernard Zalc AU - Jean-Léon Thomas AU - François Guillemot AU - Brahim Nait-Oumesmar AU - Carlos Parras Y1 - 2013/06/05 UR - http://www.jneurosci.org/content/33/23/9752.abstract N2 - 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. ER -