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首页> 外文期刊>Neuron >MEK Is a Key Regulator of Gliogenesis in the Developing Brain
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MEK Is a Key Regulator of Gliogenesis in the Developing Brain

机译：MEK是大脑发育中胶质细胞生成的关键调节剂

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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. Li et al. show that MEK/ERK signaling is important for generation of glia from neural progenitors in developing rodent forebrain. Further, excessive activation of MEK/ERK as occurs in human neurodevelopment syndromes leads to a major expansion of glial populations.
机译：我们已经定义了MEK在使用功能丧失和获得功能的小鼠遗传学调控大脑皮质发育中的神经胶质生成中的功能。在胚胎发育后期，Mek1和Mek2均缺乏的骨祖细胞无法转变为胶质形成模式，星形胶质细胞和少突胶质前体也不会出现。在探索机制中，我们发现关键的细胞因子调节的胶质生成途径被减弱。此外，Ets转录家族成员Etv5 / Erm受MEK强烈调节，Erm过表达可以挽救Mek缺失祖细胞的胶质生成潜能。值得注意的是，Mek1 / 2缺失的小鼠在出生后存活，其皮质几乎没有星形胶质细胞和少突胶质细胞，并表现出神经变性。相反，组成性活性MEK1的表达导致成年大脑中星形胶质细胞数量的大量增加。我们得出的结论是，MEK对于放射状祖细胞获得胶质生成能力至关重要，并且MEK活性水平调节着发育中的皮层的胶质生成。 Li等。结果表明，MEK / ERK信号传导对于发育中的啮齿类前脑神经元祖胶质的产生非常重要。此外，人类神经发育综合症中发生的MEK / ERK过度活化导致神经胶质种群的大量增加。

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