Departments of Ophthalmology and Visual Sciences, and Neurobiology and Anatomy, John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA.
Dev Dyn. 2012 May;241(5):941-52. doi: 10.1002/dvdy.23782.
The cell-cycle regulator Cyclin D1 is expressed in embryonic retinal progenitor cells (RPCs) and regulates their cell-cycle rate and neurogenic output. We report here that Cyclin D1 also has important functions in postnatal retinal histogenesis.
The initial production of Müller glia and bipolar cells was enhanced in Cyclin D1 knockout (Ccnd1(-/-) ) retinas. Despite a steeper than normal rate of depletion of the RPC population at embryonic ages, postnatal Ccnd1(-/-) retinas exhibited an extended window of proliferation, neurogenesis, and gliogenesis. Cyclin D3, normally confined to Müller glia, was prematurely expressed in Ccnd1(-/-) RPCs. However, Cyclin D3 did not compensate for Cyclin D1 in regulating cell-cycle kinetics or neurogenic output.
The data presented in this study along with our previous finding that Cyclin D2 was unable to completely compensate for the absence of Cyclin D1 indicate that Cyclin D1 regulates retinal histogenesis in ways not shared by the other D-cyclins.
细胞周期调控因子 Cyclin D1 存在于胚胎视网膜祖细胞（RPCs）中，调节其细胞周期率和神经发生输出。我们在此报告，Cyclin D1 在后生性视网膜组织发生中也具有重要功能。
在 Cyclin D1 敲除（Ccnd1(-/-) ）视网膜中，Müller 胶质细胞和双极细胞的初始产生增强。尽管胚胎期 RPC 群体的耗竭速度比正常情况下陡峭，但出生后 Ccnd1(-/-) 视网膜表现出增殖、神经发生和神经胶质发生的延长窗口。Cyclin D3 通常局限于 Müller 胶质细胞，但在 Ccnd1(-/-) RPC 中过早表达。然而，Cyclin D3 不能在调节细胞周期动力学或神经发生输出方面替代 Cyclin D1。
本研究中的数据以及我们之前的发现表明，Cyclin D2 不能完全替代 Cyclin D1，表明 Cyclin D1 以其他 D 型细胞周期蛋白所没有的方式调节视网膜组织发生。
