Role of the imprinted allele of the Cdkn1c gene in mouse neocortical development
Role of the imprinted allele of the Cdkn1c gene in mouse neocortical development
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DOI：
10.1038/s41598-020-58629-9
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发表时间：
2020-02-05
影响因子：
4.6
通讯作者：
Gotoh, Yukiko
中科院分区：
文献类型：
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作者：
Imaizumi, Yui;Furutachi, Shohei;Gotoh, Yukiko
印记基因只在一个等位基因中以特定来源的方式在亲本中表达。细胞周期蛋白依赖的激酶抑制因子p57(Kip2)由一个印迹基因cdkn1c编码，父亲的等位基因被沉默。然而，关于CDKN1c的父系等位基因的可能表达和功能的研究仍然很少。我们现在发现，CDKN1c基因的父系等位基因在发育中的小鼠新皮质中表达水平较低。令人惊讶的是，特定于中枢神经系统的CDKN1c基因座上父系等位基因(PAT CKO)的条件性缺失导致了大脑大小的显著缩小。此外，PAT CKO在新皮质发育过程中逐渐减少了神经干祖细胞的数量，从而减少了来自晚期神经干细胞的上层神经元的数量。因此，我们的结果表明，CDKN1c基因座的父系等位基因在新皮质发育过程中对鼻咽癌的维持起着关键作用。
Imprinted genes are expressed from only one allele in a parent of origin-specific manner. The cyclin-dependent kinase inhibitor p57(kip2) is encoded by an imprinted gene Cdkn1c, with the paternal allele being silenced. The possible expression and function of the paternal allele of Cdkn1c have remained little studied, however. We now show that the paternal allele of the Cdkn1c gene is expressed at a low level in the developing mouse neocortex. Surprisingly, the central nervous system-specific conditional deletion of the paternal allele (pat cKO) at the Cdkn1c locus resulted in a marked reduction in brain size. Furthermore, pat cKO 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 Cdkn1c locus plays a key role in maintenance of NPCs during neocortical development.