Wang Tsu-Wei, Stromberg Gregory P, Whitney Justin T, Brower Nathan W, Klymkowsky Michael W, Parent Jack M
Department of Neurology and Neuroscience Graduate Program, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
J Comp Neurol. 2006 Jul 1;497(1):88-100. doi: 10.1002/cne.20984.
Neural precursors persist throughout life in the rodent forebrain subventricular zone (SVZ) and hippocampal dentate gyrus. The regulation of persistent neural stem cells is poorly understood, in part because of the lack of neural progenitor markers. The Sox B1 subfamily of HMG-box transcription factors (Sox1-3) is expressed by precursors in the embryonic nervous system, where these factors maintain neural progenitors in an undifferentiated state while suppressing neuronal differentiation. Sox2 expression persists in germinative zones of the adult rodent brain, but Sox3 expression in the postnatal brain remains largely unexplored. Here we examine Sox3 expression in the neonatal and adult mouse brain to gain insight into its potential involvement in regulating persistent neural stem cells and neurogenesis. We also investigate Sox3 expression during expansion and neural differentiation of postnatal mouse SVZ neural stem cell and human embryonic stem cell (hESC) cultures. We find that Sox3 is expressed transiently by proliferating and differentiating neural progenitors in the SVZ-olfactory bulb pathway and dentate gyrus. Sox3 immunoreactivity also persists in specific postmitotic neuronal populations. In vitro, high Sox3 protein expression levels in undifferentiated, SVZ-derived neurospheres decline markedly with differentiation. Sox3 immunoreactivity in hESCs appears upon differentiation to neural progenitors and then decreases as cells differentiate further into neurons. These findings suggest that Sox3 labels specific stages of hESC-derived and murine neonatal and adult neural progenitors and are consistent with a role for Sox3 in neural stem cell maintenance. Persistent Sox3 expression in some mature neuronal populations suggests additional undefined roles for Sox3 in neuronal function.
神经前体细胞在啮齿动物前脑的脑室下区（SVZ）和海马齿状回中终生存在。人们对持续性神经干细胞的调控了解甚少，部分原因是缺乏神经祖细胞标志物。HMG盒转录因子的Sox B1亚家族（Sox1 - 3）在胚胎神经系统的前体细胞中表达，这些因子可维持神经祖细胞处于未分化状态，同时抑制神经元分化。Sox2在成年啮齿动物脑的生发区持续表达，但出生后脑内Sox3的表达情况在很大程度上仍未得到充分研究。在此，我们检测了新生和成年小鼠脑中Sox3的表达情况，以深入了解其在调控持续性神经干细胞和神经发生过程中的潜在作用。我们还研究了出生后小鼠SVZ神经干细胞和人胚胎干细胞（hESC）培养物在扩增和神经分化过程中Sox3的表达情况。我们发现，在SVZ - 嗅球通路和齿状回中，增殖和分化的神经祖细胞会短暂表达Sox3。Sox3免疫反应性也在特定的有丝分裂后神经元群体中持续存在。在体外，未分化的、源自SVZ的神经球中高表达的Sox3蛋白水平会随着分化而显著下降。hESCs分化为神经祖细胞时会出现Sox3免疫反应性，随后随着细胞进一步分化为神经元而降低。这些发现表明，Sox3标记了hESC来源的以及小鼠新生和成年神经祖细胞的特定阶段，这与Sox3在神经干细胞维持中的作用一致。在一些成熟神经元群体中持续存在的Sox3表达表明，Sox3在神经元功能中还有其他未明确的作用。
