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J Neurosci. 2011 Jan 19;31(3):843-50. doi: 10.1523/JNEUROSCI.3239-10.2011.

The ERK2 mitogen-activated protein kinase regulates the timing of oligodendrocyte differentiation.

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Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106, USA.


Oligodendrocyte development is tightly controlled by a variety of extracellular growth and differentiation factors. The mitogen-activated protein kinases (MAPKs), ERK1 and ERK2, are critical intracellular signaling molecules important for transducing these extracellular signals. The extracellular signal-regulated kinases (ERKs) are ubiquitously expressed, coordinately regulated, and highly similar, but Erk2 deletion in mice is embryonic lethal whereas Erk1 deletion is not. Several studies have suggested that MAPK signaling is important for oligodendrocyte differentiation, although specific roles for the two ERK isoforms have not been investigated. In this study, we deleted Erk2 in the developing mouse cortex from GFAP-expressing radial glia that generate neurons and oligodendrocytes. In vitro analysis revealed that loss of ERK2 resulted in fewer galactocerebroside-expressing mature oligodendrocytes in cortical cultures. In vivo, a delay in the expression of the myelin protein MBP was observed in the corpus callosum at postnatal day 10 (P10). In contrast, Erk1 deletion did not affect oligodendrocyte differentiation. By P21, MBP expression was restored to wild-type levels, demonstrating that the loss of ERK2 results in a delay but not a complete arrest in the appearance of differentiated oligodendrocytes in vivo. Importantly, both the proliferation and total number of oligodendrocyte progenitor cells (OPCs) appeared normal in the Erk2 conditional knock-out cortex, demonstrating that ERK2 plays a specific role in the timing of forebrain myelination but is not critical for the proliferation or survival of OPCs. Oligodendrocyte-specific deletion of Erk2 also resulted in decreased levels of MBP, indicating a cell-autonomous effect of ERK2 in the oligodendrocyte lineage.

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