Malaterre Jordane, Mantamadiotis Theo, Dworkin Sebastian, Lightowler Sally, Yang Qing, Ransome Mark I, Turnley Ann M, Nichols Nancy R, Emambokus Nikla R, Frampton Jon, Ramsay Robert G
Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Stem Cells. 2008 Jan;26(1):173-81. doi: 10.1634/stemcells.2007-0293. Epub 2007 Sep 27.
Ongoing production of neurons in adult brain is restricted to specialized neurogenic niches. Deregulated expression of genes controlling homeostasis of neural progenitor cell division and/or their microenvironment underpins a spectrum of brain pathologies. Using conditional gene deletion, we show that the proto-oncogene c-myb regulates neural progenitor cell proliferation and maintains ependymal cell integrity in mice. These two cellular compartments constitute the neurogenic niche in the adult brain. Brains devoid of c-Myb showed enlarged ventricular spaces, ependymal cell abnormalities, and reduced neurogenesis. Neural progenitor cells lacking c-Myb showed a reduced intrinsic proliferative capacity and reduction of Sox-2 and Pax-6 expression. These data point to an important role for c-Myb in the neurogenic niche of the adult brain.
成人大脑中神经元的持续生成仅限于特定的神经发生微环境。控制神经祖细胞分裂及其微环境稳态的基因表达失调是一系列脑部疾病的基础。通过条件性基因缺失,我们发现原癌基因c-myb调节小鼠神经祖细胞的增殖并维持室管膜细胞的完整性。这两个细胞区室构成了成人大脑中的神经发生微环境。缺乏c-Myb的大脑表现出脑室空间扩大、室管膜细胞异常和神经发生减少。缺乏c-Myb的神经祖细胞表现出内在增殖能力降低以及Sox-2和Pax-6表达减少。这些数据表明c-Myb在成人大脑的神经发生微环境中具有重要作用。