Cerebellar cortical lamination and foliation require cyclin A2.
Cerebellar cortical lamination and foliation require cyclin A2.
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DOI：
10.1016/j.ydbio.2013.10.019
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发表时间：
2014-01-15
影响因子：
2.7
通讯作者：
Rowitch, David
中科院分区：
文献类型：
--
作者：
Otero, Jose Javier;Kalaszczynska, Ilona;Michowski, Wojciech;Wong, Michael;Gygli, Patrick Edwin;Gokozan, Hamza Numan;Griveau, Amelie;Odajima, Junko;Czeisler, Catherine;Catacutan, Fay Patsy;Murnen, Alice;Schueller, Ulrich;Sicinski, Piotr;Rowitch, David
关键词：
哺乳动物基因组编码两个A型细胞周期蛋白，它们被认为是细胞周期的潜在冗余但必不可少的调节因子。在这里，我们测试了小脑发育过程中对细胞周期蛋白A1和A2功能的要求。神经前体细胞周期蛋白A1/A2的复合条件性缺失可导致小脑发育不良、小脑颗粒神经元前体细胞(CGNP)增殖减少和浦肯野(PC)神经元损伤。Cyclin A2的单独缺失表现出相同的表型，表明Cyclin A1不能补偿神经前体细胞中Cyclin A2的丢失。细胞周期蛋白A2的缺失导致胚胎早期的细胞凋亡增加，但在出生后的各时间点并不明显。相反，VZ/SVZ的神经前体细胞没有经历更多的凋亡，这表明VZ/SVZ来源的神经前体细胞和菱形LIP来源的前体细胞对细胞周期蛋白A2的需求不同。在CGNP中，Cyclin A2或SHH增殖靶点Nmyc的条件性敲除也导致PC神经元损伤。尽管细胞周期蛋白E1在成纤维细胞中可以补偿细胞周期蛋白A2的功能，并且在细胞周期蛋白A2缺失的小脑中表达上调，但细胞周期蛋白E1的表达不能补偿细胞周期蛋白A2功能的丧失。
The mammalian genome encodes two A-type cyclins, which are considered potentially redundant yet essential regulators of the cell cycle. Here, we tested requirements for cyclin A1 and cyclin A2 function in cerebellar development. Compound conditional loss of cyclin A1/A2 in neural progenitors resulted in severe cerebellar hypoplasia, decreased proliferation of cerebellar granule neuron progenitors (CGNP), and Purkinje (PC) neuron dyslamination. Deletion of cyclin A2 alone showed an identical phenotype, demonstrating that cyclin A1 does not compensate for cyclin A2 loss in neural progenitors. Cyclin A2 loss lead to increased apoptosis at early embryonic time points but not at post-natal time points. In contrast, neural progenitors of the VZ/SVZ did not undergo increased apoptosis, indicating that VZ/SVZ-derived and rhombic lip-derived progenitor cells show differential requirements to cyclin A2. Conditional knockout of cyclin A2 or the SHH proliferative target Nmyc in CGNP also resulted in PC neuron dyslamination. Although cyclin E1 has been reported to compensate for cyclin A2 function in fibroblasts and is upregulated in cyclin A2 null cerebella, cyclin E1 expression was unable to compensate for loss-of cyclin A2 function.
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影响因子：
15.9
作者：
Heine, Vivi M.;Rowitch, David H.
通讯作者：
Rowitch, David H.
影响因子：
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Jirawatnotai S;Hu Y;Michowski W;Elias JE;Becks L;Bienvenu F;Zagozdzon A;Goswami T;Wang YE;Clark AB;Kunkel TA;van Harn T;Xia B;Correll M;Quackenbush J;Livingston DM;Gygi SP;Sicinski P
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Sicinski P
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4.6
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Rowitch, DH
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DOREE, M
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通讯作者：
Joyner, AL