Roles of cell cycle regulatory protein p27 in murine neocortical histogenesis

细胞周期调节蛋白p27在小鼠新皮质组织发生中的作用

基本信息

批准号：
13670837
负责人：
TAKAHASHI Takao
金额：
$ 2.18万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670837/
关键词：
cerebral histogenesis cell cycle development mouse neuronal progenitor CDK 神経系前駆細胞

项目摘要

p27^<kip1> is a cell cycle regulatory protein that inhibits G1 phase progression and induces cell differentiation. In p27^<kip1> knockout mouse (p27KO), the size of the brain is increased by about 30 %. We previously observed that both thickness and number of non-GABAergic neurons in the cortical layers II-IV were significantly increased in p27KO as compared to the WT littermates. These suggest that output from the NPCs in the middle to late period of neuronogenesis was increased by loss of function of p27^<kip1>. To investigate the histogenetic mechanisms of the cortical malformation in p27KO, we have studied proliferation and differentiation characteristics of the NPCs in the p27KO at embryonic day 14 (E14).The cell cycle length of the NPCs at E14 was indistinguishable between p27KO and WT. However, the number of the newly differentiated neurons (Q cells) at E14 was reduced in p27KO. The consequence is that there is proliferative augmentation of NPCs in the p27KO animals at E14. The distribution pattern of the Q cells in the p27KO was also abnormal. The exit behavior of Q cells from the proliferative epithelium is bimodal in both genotypes ; partitioned into rapidly and slowly exiting subpopulations. The reduction in the Q fraction in the p27KO is assignable entirely to the rapidly exiting subset of Q cells.The neocortical malformation in the p27KO is likely to be attributable to an abnormal pattern of the ascent of Q fraction during the middle phase of neuronogenetic interval.

p27^<kip1>是一种细胞周期调节蛋白，可抑制G1相进展并诱导细胞分化。在p27^<kip1>基因敲除小鼠（P27KO）中，大脑的大小增加了约30％。我们先前观察到，与WT同窝同els相比，P27KO的皮质层II-IV中的厚度和非gaba能神经元的数量显着增加。这些表明，通过p27^<kip1>的功能丧失，在神经发生的中部至后期发出的NPC的输出增加了。为了研究p27KO中皮质畸形的组织遗传机制，我们研究了p27ko在胚胎第14天（E14）中NPC的增殖和分化特征（E14）。但是，在P27KO中，E14的新分化神经元（Q细胞）的数量减少。结果是，在E14的P27KO动物中，NPC会增强。 p27KO中Q细胞的分布模式也异常。在两种基因型中，Q细胞从增殖上皮的退出行为都是双峰的。迅速划分为慢慢退出亚群。 P27KO中Q分数的减少完全可以完全分配给Q细胞的快速退出子集。p27KO中的新皮质畸形可能归因于神经发育间隔中Q分数上升的异常模式。