E2F1 Works as a Cell Cycle Suppressor in Mature Neurons
E2F1 Works as a Cell Cycle Suppressor in Mature Neurons
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DOI：
10.1523/jneurosci.3681-07.2007
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发表时间：
2007-11
期刊：
影响因子：
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通讯作者：
Li Wang;Rong Wang;K. Herrup
中科院分区：
文献类型：
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作者：
Li Wang;Rong Wang;K. Herrup
神经元是高度分化的细胞，通常不会进入细胞周期。如果他们这样做，结果通常是死亡，而不是分裂。例如，交错和倾斜突变小鼠的小脑颗粒神经元在死亡前启动类似细胞周期的过程。 E2F1是一种促进细胞周期进程的转录因子。由于E2F1也参与细胞凋亡，我们培育了双突变体（E2f1−/−；staggerer和E2f1−/−；luncher）来评估其在体内小脑颗粒细胞细胞周期相关死亡中的作用。我们发现在任一双突变体中颗粒细胞周期启动和细胞死亡均没有显着改变。然而，出生后第 10 天后，发现 E2f1−/− 和 E2f1+/- 动物整个 CNS 的神经元表达细胞周期蛋白并复制其 DNA。虽然 Map2 和突触蛋白 1 染色几乎没有改变，但 1 岁时浦肯野细胞树突中的钙结合蛋白减少，表明突变细胞也经历了缓慢、微妙的萎缩。这些事件是细胞自主的，因为培养的 E2f1−/− 皮质神经元在体外“循环”，而野生型神经元则不然。我们的结果表明，在成熟的 CNS 神经元中，E2F1 作为细胞周期抑制因子发挥作用。
Neurons are highly differentiated cells that normally never enter a cell cycle; if they do, the result is usually death, not division. For example, cerebellar granule neurons in staggerer and lurcher mutant mice initiate a cell cycle-like process just before they die. E2F1 is a transcription factor that promotes cell cycle progression. Because E2F1 is also involved in apoptosis, we bred double mutants (E2f1−/−; staggerer and E2f1−/−; lurcher) to assess its role in the cell cycle-related death of cerebellar granule cells in vivo. We found neither granule cell cycle initiation nor cell death was significantly altered in either double mutant. However, after postnatal day 10, neurons throughout the CNS of E2f1−/− and E2f1+/− animals were found to express cell cycle proteins and replicate their DNA. Whereas Map2 and synapsin1 staining are little altered, there is a reduction of calbindin in Purkinje cell dendrites at 1 year of age, suggesting that the mutant cells also undergo a slow, subtle atrophy. These events are cell autonomous, because cultured E2f1−/− cortical neurons “cycle” in vitro, whereas wild-type neurons do not. Our results suggest that, in mature CNS neurons, E2F1 functions as a cell cycle suppressor.