p27Kip1 regulates cell cycle withdrawal of late multipotent progenitor cells in the mammalian retina
p27Kip1 regulates cell cycle withdrawal of late multipotent progenitor cells in the mammalian retina
复制标题
p27Kip1调控哺乳动物视网膜中晚期多能祖细胞的细胞周期退出
DOI：
10.1006/dbio.2000.9622
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发表时间：
2000-03-15
影响因子：
2.7
通讯作者：
Reh, TA
中科院分区：
文献类型：
--
作者：
Levine, EM;Close, J;Reh, TA
细胞周期蛋白依赖性激酶抑制剂蛋白p27（Kip1），是必要的细胞周期撤退的时间，在视神经少突胶质细胞的终末分化之前。虽然p27（Kip1）在发育中的中枢神经系统中广泛表达，但尚不清楚这种蛋白质是否在神经元分化中具有类似的作用。为了解决这个问题，我们研究了p27（Kip1）在发育中的视网膜，一个良好的特征部分的中枢神经系统的表达和功能。p27（Kip1）以与大多数视网膜细胞类型的分化开始一致的模式表达。体外分析表明，p27（Kip1）在视网膜细胞中的积累与细胞周期的退出和分化相关，当过表达时，p27（Kip1）抑制祖细胞的增殖。此外，光感受器和Muller神经胶质细胞的组织发生在p27（Kip1）缺陷小鼠的视网膜中扩展。最后，我们用细胞类型特异性标记物检查了p27（Kip1）缺陷小鼠的成人视网膜发育不良。相反，以前的建议，发育不良是由于过量生产的光感受器，我们认为，发育不良是由于反应性穆勒胶质细胞的感光细胞外段层的位移。这些结果表明，p27（Kip1）是控制多能中枢神经系统祖细胞退出细胞周期的决定的分子机制的一部分。第二，有丝分裂后的Muller胶质细胞有一个新的和内在的需要p27（Kip1）在维持其分化状态。(C)北京大学出版社.
The cyclin-dependent kinase inhibitor protein, p27(Kip1), is necessary for the timing of cell cycle withdrawal that precedes terminal differentiation in oligodendrocytes of the optic nerve. Although p27(Kip1) is widely expressed in the developing central nervous system, it is not known whether this protein has a similar role in neuronal differentiation. To address this issue, we have examined the expression and function of p27(Kip1) in the developing retina, a well-characterized part of the central nervous system. p27(Kip1) is expressed in a pattern coincident with the onset of differentiation of most retinal cell types. In vitro analyses show that p27(Kip1) accumulation in retinal cells correlates with cell cycle withdrawal and differentiation, and when overexpressed, p27(Kip1) inhibits proliferation of the progenitor cells. Furthermore, the histogenesis of photoreceptors and Muller glia is extended in the retina of p27(Kip1)-deficient mice. Finally, we examined the adult retinal dysplasia in p27(Kip1)-deficient mice with cell-type-specific markers. Contrary to previous suggestions that the dysplasia is caused by excess production of photoreceptors, we suggest that the dysplasia is due to the displacement of reactive Muller glia into the layer of photoreceptor outer segments. These results demonstrate that p27(Kip1) is part of the molecular mechanism that controls the decision of multipotent central nervous system progenitors to withdraw from the cell cycle. Second, postmitotic Muller glia have a novel and intrinsic requirement for p27(Kip1) in maintaining their differentiated state. (C) 2000 Academic Press.