2012年9月3日 訊 /生物谷BIOON/ --神經(jīng)干細(xì)胞的不對稱分裂是神經(jīng)發(fā)育的一個基礎(chǔ)特征，對這種不對稱分裂進(jìn)行錯誤調(diào)節(jié)會導(dǎo)致大腦異?；蚰X瘤產(chǎn)生,。在一次不對稱分裂期間，確定子細(xì)胞命運的分子決定物會被優(yōu)先分離到一個子細(xì)胞中,。因此,，對科學(xué)家們而言，一個重要的目標(biāo)就是鑒定出神經(jīng)祖細(xì)胞(neural progenitor cell)中的不對稱決定物(asymmetric determinant),。
在當(dāng)前這項研究中,，來自美國紐約再生研究基金會神經(jīng)干細(xì)胞研究所、紐約州立大學(xué)和奧地利維也納醫(yī)科大學(xué)的研究人員證實雙鏈RNA結(jié)合蛋白Stau2在發(fā)育中的小鼠皮層內(nèi)的神經(jīng)祖細(xì)胞分裂期間,，是不對稱分布的,，而且與一小部分RNA一起被優(yōu)先分離到Tbr2陽性的成神經(jīng)細(xì)胞子細(xì)胞之中。抑制Stau2表達(dá)促進(jìn)神經(jīng)祖細(xì)胞分化,，而它的過量表達(dá)會大量產(chǎn)生分布在腦室周圍的神經(jīng)元,，這就證明它在正常的皮層發(fā)育中發(fā)揮著重要的功能性作用,。
這些發(fā)現(xiàn)人們更加深刻地認(rèn)識哺乳動物神經(jīng)干細(xì)胞的維持自我更新和進(jìn)行分化的機制，從而為未來開發(fā)出潛在的療法來治療神經(jīng)退化性方面的疾病打下基礎(chǔ),。相關(guān)研究結(jié)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.
