BACKGROUND Cyclin-dependent kinase (CDK) inhibitors play an important role in regulating cell cycle progression, cell cycle exit and cell differentiation. p27KIP1 (p27), one of the major CDK inhibitors in the retina, has been shown to control the timing of cell cycle exit of retinal progenitors. However, the precise role of this protein in retinal development remains largely unexplored. We thus analyzed p27-deficient mice to characterize the effects of p27 loss on proliferation, differentiation, and survival of retinal cells. METHODS Expression of p27 in the developing and mature mouse retina was analyzed by immunohistochemistry using antibodies against p27 and cell type-specific markers. Cell proliferation and differentiation were examined in the wild-type and p27-deficient retinas by immunohistochemistry using various cell cycle and differentiation markers. RESULTS All postmitotic retinal cell types expressed p27 in the mouse retinas. p27 loss caused extension of the period of proliferation in the developing retinas. This extra proliferation was mainly due to ectopic cell cycle reentry of differentiating cells including bipolar cells, Müller glial cells and cones, rather than persistent division of progenitors as previously suggested. Aberrant cell cycle activity of cones was followed by cone death resulting in a significant reduction in cone number in the mature p27-deficient retinas. CONCLUSIONS Although expressed in all retinal cell types, p27 is required to maintain the quiescence of specific cell types including bipolar cells, Müller glia, and cones while it is dispensable for preventing cell cycle reentry in other cell types.

中文翻译：

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p27KIP1丢失对视网膜发育的细胞类型特异性影响。

背景技术细胞周期蛋白依赖性激酶（CDK）抑制剂在调节细胞周期进程，细胞周期退出和细胞分化中起重要作用。已显示p27KIP1（p27）是视网膜中的主要CDK抑制剂之一，可控制视网膜祖细胞退出细胞周期的时间。然而，该蛋白在视网膜发育中的确切作用在很大程度上尚待探索。因此，我们分析了p27缺陷小鼠，以表征p27缺失对视网膜细胞增殖，分化和存活的影响。方法使用针对p27的抗体和细胞类型特异性标记物，通过免疫组织化学分析p27在发育中和成熟小鼠视网膜中的表达。使用各种细胞周期和分化标记，通过免疫组织化学检查了野生型和p27缺陷型视网膜中的细胞增殖和分化。结果所有有丝分裂后视网膜细胞类型在小鼠视网膜中均表达p27。p27丢失导致发育中的视网膜的增殖期延长。这种额外的增殖主要是由于分化细胞（包括双极细胞，Müller胶质细胞和视锥细胞）的异位细胞周期再进入，而不是先前提出的祖细胞的持久分裂。视锥细胞的异常细胞周期活性随后是视锥细胞死亡，导致成熟的p27缺陷型视网膜的视锥细胞数目显着减少。结论尽管在所有视网膜细胞类型中都有表达，