title: MEK Is a Key Regulator of Gliogenesis in the Developing Brain.
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.
authors.affiliation: UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Jason M
authors.initials: JM
authors.lastname: Newbern
authors.forename: Yaohong
authors.initials: Y
authors.lastname: Wu
authors.forename: Meghan
authors.initials: M
authors.lastname: Morgan-Smith
authors.forename: Jian
authors.initials: J
authors.lastname: Zhong
authors.forename: Jean
authors.initials: J
authors.lastname: Charron
authors.forename: William D
authors.initials: WD
authors.lastname: Snider
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D018274:Electroporation; D004622:Embryo, Mammalian; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D048369:MAP Kinase Kinase 1 / Q000172:deficiency* / Q000235:genetics; D048370:MAP Kinase Kinase 2 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000187:drug effects; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D020934:Ciliary Neurotrophic Factor; D004268:DNA-Binding Proteins; C513242:Etv5 protein, mouse; D027341:Excitatory Amino Acid Transporter 1; D005136:Eye Proteins; D018398:Homeodomain Proteins; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482127:Map2k1 protein, mouse; C482129:Map2k2 protein, mouse