Dynamic Pax6 expression during the neurogenic cell cycle influences proliferation and cell fate choices of retinal progenitors.
Dynamic Pax6 expression during the neurogenic cell cycle influences proliferation and cell fate choices of retinal progenitors.
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DOI：
10.1186/1749-8104-4-32
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发表时间：
2009-08-17
影响因子：
3.6
通讯作者：
Yang XJ
中科院分区：
文献类型：
--
作者：
Hsieh YW;Yang XJ
Pax 6是视网膜祖细胞增殖和多能性的关键蛋白。然而，与各种视网膜神经元的产生相关的Pax 6蛋白表达的时间变化尚未被表征为关于细胞周期。在这里，我们研究鸡视网膜祖细胞之间的Pax 6表达的动态变化，因为他们通过神经细胞周期的进展，并确定改变Pax 6水平对视网膜发生的影响。我们提供的证据表明，在preneurogenic神经原性的过渡，Pax 6蛋白水平在增殖祖细胞下调。神经原性视网膜祖细胞保留相对低水平的Pax 6蛋白，而有丝分裂后神经元以细胞类型特异性方式升高或消除Pax 6表达。细胞成像和细胞周期分析表明，在细胞周期的S期的神经源性祖细胞含有低水平的Pax 6蛋白，而一个子集的祖细胞表现出不同水平的Pax 6蛋白进入G2期的细胞周期。我们还表明，M期细胞含有不同水平的Pax 6，和一些相关的发病早期神经元标记物的表达，预测细胞周期退出和细胞命运的承诺。此外，升高或敲低Pax 6都会减弱细胞增殖并导致细胞死亡增加。降低Pax 6会降低视网膜神经节细胞的发生，并增强视锥光感受器和无长突中间神经元的产生，而升高Pax 6会抑制视锥光感受器和无长突细胞的命运。这些研究首次证明了Pax 6蛋白表达的定量变化在preneurogenic神经原性的过渡和神经原性细胞周期期间。结果表明，Pax 6蛋白水平在增殖的祖细胞中受到严格控制。维持相对低的Pax 6蛋白水平对于S期再进入是必要的，而在细胞周期的G2/M期期间Pax 6蛋白的快速积累或减少可能是特定神经元命运所需的。因此，这些研究结果提供了新的见解Pax 6蛋白的动态调节神经祖细胞和神经元命运决定的时间框架。
The paired homeobox protein Pax6 is essential for proliferation and pluripotency of retinal progenitors. However, temporal changes in Pax6 protein expression associated with the generation of various retinal neurons have not been characterized with regard to the cell cycle. Here, we examine the dynamic changes of Pax6 expression among chicken retinal progenitors as they progress through the neurogenic cell cycle, and determine the effects of altered Pax6 levels on retinogenesis. We provide evidence that during the preneurogenic to neurogenic transition, Pax6 protein levels in proliferating progenitor cells are down-regulated. Neurogenic retinal progenitors retain a relatively low level of Pax6 protein, whereas postmitotic neurons either elevate or extinguish Pax6 expression in a cell type-specific manner. Cell imaging and cell cycle analyses show that neurogenic progenitors in the S phase of the cell cycle contain low levels of Pax6 protein, whereas a subset of progenitors exhibits divergent levels of Pax6 protein upon entering the G2 phase of the cell cycle. We also show that M phase cells contain varied levels of Pax6, and some correlate with the onset of early neuronal marker expression, forecasting cell cycle exit and cell fate commitment. Furthermore, either elevating or knocking down Pax6 attenuates cell proliferation and results in increased cell death. Reducing Pax6 decreases retinal ganglion cell genesis and enhances cone photoreceptor and amacrine interneuron production, whereas elevating Pax6 suppresses cone photoreceptor and amacrine cell fates. These studies demonstrate for the first time quantitative changes in Pax6 protein expression during the preneurogenic to neurogenic transition and during the neurogenic cell cycle. The results indicate that Pax6 protein levels are stringently controlled in proliferating progenitors. Maintaining a relatively low Pax6 protein level is necessary for S phase re-entry, whereas rapid accumulation or reduction of Pax6 protein during the G2/M phase of the cell cycle may be required for specific neuronal fates. These findings thus provide novel insights on the dynamic regulation of Pax6 protein among neurogenic progenitors and the temporal frame of neuronal fate determination.
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影响因子：
--
作者：
Manuel M;Pratt T;Liu M;Jeffery G;Price DJ
通讯作者：
Price DJ
影响因子：
16.2
作者：
HOLT, CE;BERTSCH, TW;HARRIS, WA
通讯作者：
HARRIS, WA
影响因子：
64.8
作者：
HILL, RE;FAVOR, J;VANHEYNINGEN, V
通讯作者：
VANHEYNINGEN, V
影响因子：
4.6
作者：
Hashimoto, Takao;Zhang, Xiang-Mei;Yang, Xian-Jie
通讯作者：
Yang, Xian-Jie
影响因子：
2.7
作者：
Kim, J;Lauderdale, JD
通讯作者：
Lauderdale, JD