Akirin2 is essential for the formation of the cerebral cortex.
Akirin2 is essential for the formation of the cerebral cortex.
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DOI：
10.1186/s13064-016-0076-8
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发表时间：
2016-11-21
影响因子：
3.6
通讯作者：
Weiner JA
中科院分区：
文献类型：
--
作者：
Bosch PJ;Fuller LC;Sleeth CM;Weiner JA
对背端端祖细胞行为的适当时空调控是形成高度组织化的六层大脑皮层的先决条件。细胞过早分化、细胞周期中断、过度凋亡和/或不正确的神经元迁移信号可产生破坏性影响，导致包括小头畸形和/或无脑畸形在内的许多神经发育障碍。虽然在大脑皮层发育过程中许多关键角色的基因编码已经被确定，但我们的理解仍然不完整。我们发现编码Akirin2（一种小核蛋白）的基因在胚胎端脑中表达。越来越多的证据表明，Akirin2作为转录因子（包括Twist和NF-κB蛋白）和BAF （SWI/SNF）染色质重塑机制之间的桥梁，调节基因表达模式。在小鼠中，Akirin2的组成性敲除是早期胚胎致死的，而B细胞的限制性缺失导致增殖和细胞存活中断。我们通过将含有固定Akirin2等位基因的小鼠与Emx1-Cre转基因系杂交，产生了皮质限制性的Akirin2基因敲除，并使用原位杂交、EdU标记和免疫组织化学评估了所产生的胚胎。绝大多数Akirin2突变体不能在出生后存活，并表现出极端的小头畸形，几乎没有背端脑组织，没有可识别的皮层。这主要是由于早期皮质祖细胞的大量死亡，这种死亡开始于胚胎日(E)10，在Emx1-Cre活跃后不久。免疫染色和使用EdU标记的细胞周期分析表明，akirin2缺失的祖细胞不能正常增殖，产生较少的神经元，并发生广泛的凋亡。在Akirin2突变体中产生的所有神经元也通过E12发生凋亡。对Wnt3a和wnt应答基因的原位杂交表明，在Akirin2缺失的小鼠中，皮质边缘的形成和/或功能存在缺陷。此外，脑室顶端表面被破坏，发现sox2阳性祖细胞“溢出”到侧脑室。我们的数据证明了Akirin2在早期皮质发育中的作用，并且鉴于其已知的核作用，表明它可能调节早期祖细胞行为和皮质神经元产生的关键基因表达模式。本文的在线版本（doi:10.1186/s13064-016-0076-8）包含补充材料，可供授权用户使用。
The proper spatial and temporal regulation of dorsal telencephalic progenitor behavior is a prerequisite for the formation of the highly-organized, six-layered cerebral cortex. Premature differentiation of cells, disruption of cell cycle timing, excessive apoptosis, and/or incorrect neuronal migration signals can have devastating effects, resulting in a number of neurodevelopmental disorders involving microcephaly and/or lissencephaly. Though genes encoding many key players in cortical development have been identified, our understanding remains incomplete. We show that the gene encoding Akirin2, a small nuclear protein, is expressed in the embryonic telencephalon. Converging evidence indicates that Akirin2 acts as a bridge between transcription factors (including Twist and NF-κB proteins) and the BAF (SWI/SNF) chromatin remodeling machinery to regulate patterns of gene expression. Constitutive knockout of Akirin2 is early embryonic lethal in mice, while restricted loss in B cells led to disrupted proliferation and cell survival. We generated cortex-restricted Akirin2 knockouts by crossing mice harboring a floxed Akirin2 allele with the Emx1-Cre transgenic line and assessed the resulting embryos using in situ hybridization, EdU labeling, and immunohistochemistry. The vast majority of Akirin2 mutants do not survive past birth, and exhibit extreme microcephaly, with little dorsal telencephalic tissue and no recognizable cortex. This is primarily due to massive cell death of early cortical progenitors, which begins at embryonic day (E)10, shortly after Emx1-Cre is active. Immunostaining and cell cycle analysis using EdU labeling indicate that Akirin2-null progenitors fail to proliferate normally, produce fewer neurons, and undergo extensive apoptosis. All of the neurons that are generated in Akirin2 mutants also undergo apoptosis by E12. In situ hybridization for Wnt3a and Wnt-responsive genes suggest defective formation and/or function of the cortical hem in Akirin2 null mice. Furthermore, the apical ventricular surface becomes disrupted, and Sox2-positive progenitors are found to “spill” into the lateral ventricle. Our data demonstrate a previously-unsuspected role for Akirin2 in early cortical development and, given its known nuclear roles, suggest that it may act to regulate gene expression patterns critical for early progenitor cell behavior and cortical neuron production. The online version of this article (doi:10.1186/s13064-016-0076-8) contains supplementary material, which is available to authorized users.
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akirin是减数分裂前期 I 的二分裂二价结构和突触复合体解体所必需的。
影响因子：
3.3
作者：
Clemons AM;Brockway HM;Yin Y;Kasinathan B;Butterfield YS;Jones SJ;Colaiácovo MP;Smolikove S
通讯作者：
Smolikove S
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.15252/embj.201488456
发表时间：
2014-10-16
期刊：
The EMBO journal
影响因子：
--
作者：
Bonnay F;Nguyen XH;Cohen-Berros E;Troxler L;Batsche E;Camonis J;Takeuchi O;Reichhart JM;Matt N
通讯作者：
Matt N
DOI：
10.1523/jneurosci.2456-10.2011
发表时间：
2011-04-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Boersma MC;Dresselhaus EC;De Biase LM;Mihalas AB;Bergles DE;Meffert MK
通讯作者：
Meffert MK
影响因子：
4.6
作者：
Caronia-Brown, Giuliana;Yoshida, Michio;Grove, Elizabeth A.
通讯作者：
Grove, Elizabeth A.