2012年9月3日 讯 /生物谷BIOON/ --神经干细胞的不对称分裂是神经发育的一个基础特征，对这种不对称分裂进行错误调节会导致大脑异常或脑瘤产生。在一次不对称分裂期间，确定子细胞命运的分子决定物会被优先分离到一个子细胞中。因此，对科学家们而言，一个重要的目标就是鉴定出神经祖细胞(neural progenitor cell)中的不对称决定物(asymmetric determinant)。
在当前这项研究中，来自美国纽约再生研究基金会神经干细胞研究所、纽约州立大学和奥地利维也纳医科大学的研究人员证实双链RNA结合蛋白Stau2在发育中的小鼠皮层内的神经祖细胞分裂期间，是不对称分布的，而且与一小部分RNA一起被优先分离到Tbr2阳性的成神经细胞子细胞之中。抑制Stau2表达促进神经祖细胞分化，而它的过量表达会大量产生分布在脑室周围的神经元，这就证明它在正常的皮层发育中发挥着重要的功能性作用。
这些发现人们更加深刻地认识哺乳动物神经干细胞的维持自我更新和进行分化的机制，从而为未来开发出潜在的疗法来治疗神经退化性方面的疾病打下基础。相关研究结果刊登在Cell Stem Cell期刊上。(生物谷Bioon.com)
doi: 10.1016/j.stem.2012.06.006
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Asymmetric Segregation of the Double-Stranded RNA Binding Protein Staufen2 during Mammalian Neural Stem Cell Divisions Promotes Lineage Progression
Gretchen Kusek, Melissa Campbell, Frank Doyle, Scott A. Tenenbaum, Michael Kiebler, Sally Temple
Asymmetric cell divisions are a fundamental feature of neural development, and misregulation can lead to brain abnormalities or tumor formation. During an asymmetric cell division, molecular determinants are segregated preferentially into one daughter cell to specify its fate. An important goal is to identify the asymmetric determinants in neural progenitor cells, which could be tumor suppressors or inducers of specific neural fates. Here, we show that the double-stranded RNA-binding protein Stau2 is distributed asymmetrically during progenitor divisions in the developing mouse cortex, preferentially segregating into the Tbr2+ neuroblast daughter, taking with it a subset of RNAs. Knockdown of Stau2 stimulates differentiation and overexpression produces periventricular neuronal masses, demonstrating its functional importance for normal cortical development. We immunoprecipitated Stau2 to examine its cargo mRNAs, and found enrichment for known asymmetric and basal cell determinants, such as Trim32, and identified candidates, including a subset involved in primary cilium function.
