Role of the imprinted allele of the p57Kip2 gene in mouse neocortical development
Role of the imprinted allele of the p57Kip2 gene in mouse neocortical development
复制标题
p57Kip2基因印记等位基因在小鼠新皮质发育中的作用
DOI：
10.1101/737692
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Gotoh Yukiko
中科院分区：
文献类型：
--
作者：
Imaizumi Yui;Furutachi Shohei;Watanabe Tomoyuki;Miya Hiroaki;Kawaguchi Daichi;Gotoh Yukiko
印记基因仅从一个等位基因以来源特异性的方式表达。细胞周期蛋白依赖性激酶抑制剂p57 Kip2（p57）由一个印记基因编码，父亲的等位基因被沉默。然而，对p57的父系等位基因的可能表达和功能的研究仍然很少。我们现在表明，p57基因的父系等位基因在发育中的小鼠新皮层中以低水平表达。令人惊讶的是，中枢神经系统特异性条件性删除p57基因座上的父方等位基因（patcKO）导致脑体积显著减小。此外，patcKO在新皮层发育过程中逐渐减少神经干祖细胞（NPC）的数量，从而减少了来自晚期NPC的上层神经元的数量。因此，我们的研究结果表明，父系等位基因的p57基因座发挥了关键作用，在新皮层发育过程中的NPC的维护。
Imprinted genes are expressed from only one allele in a parent of origin–specific manner. The cyclin-dependent kinase inhibitor p57Kip2(p57) is encoded by an imprinted gene, with the paternal allele being silenced. The possible expression and function of the paternal allele of p57 have remained little studied, however. We now show that the paternal allele of the p57 gene is expressed at a low level in the developing mouse neocortex. Surprisingly, the central nervous system-specific conditional deletion of the paternal allele (patcKO) at the p57 locus resulted in a marked reduction in brain size. Furthermore,patcKO gradually reduced the number of neural stem-progenitor cells (NPCs) during neocortical development, and thus reduced the number of upper-layer neurons, which were derived from late-stage NPCs. Our results thus show that the paternal allele of the p57 locus plays a key role in maintenance of NPCs during neocortical development.