MEK Is a Key Regulator of Gliogenesis in the Developing Brain

Xiaoyan Li, Jason M. Newbern, Yaohong Wu, Meghan Morgan-Smith, Jian Zhong, Jean Charron, William D. Snider

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

We have defined functions of MEK in regulating gliogenesis in developing cerebral cortex using loss- and gain-of-function mouse genetics. Radial progenitors deficient in both Mek1 and Mek2 fail to transition to the gliogenic mode in late embryogenesis, and astrocyte and oligodendroglial precursors fail to appear. In exploring mechanisms, we found that the key cytokine-regulated gliogenic pathway is attenuated. Further, the Ets transcription family member Etv5/Erm is strongly regulated by MEK and Erm overexpression can rescue the gliogenic potential of Mek-deleted progenitors. Remarkably, Mek1/2-deleted mice surviving postnatally exhibit cortices almost devoid of astrocytes and oligodendroglia and exhibit neurodegeneration. Conversely, expression of constitutively active MEK1 leads to a major increase in numbers of astrocytes in the adult brain. We conclude that MEK is essential for acquisition of gliogenic competence by radial progenitors and that levels of MEK activity regulate gliogenesis in the developing cortex.

Original languageEnglish (US)
Pages (from-to)1035-1050
Number of pages16
JournalNeuron
Volume75
Issue number6
DOIs
StatePublished - Sep 20 2012
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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    Li, X., Newbern, J. M., Wu, Y., Morgan-Smith, M., Zhong, J., Charron, J., & Snider, W. D. (2012). MEK Is a Key Regulator of Gliogenesis in the Developing Brain. Neuron, 75(6), 1035-1050. https://doi.org/10.1016/j.neuron.2012.08.031