Shh directs cell‐cycle exit by activating p57Kip2 in the zebrafish retina
Shh directs cell‐cycle exit by activating p57Kip2 in the zebrafish retina
复制标题
DOI：
10.1038/sj.embor.7400416
复制
发表时间：
2005-06
期刊：
影响因子：
7.7
通讯作者：
Alena Shkumatava;C. Neumann
中科院分区：
文献类型：
--
作者：
Alena Shkumatava;C. Neumann
Hedgehog (Hh) 信号蛋白家族控制动物发育过程中的分化和增殖。先前的研究表明，Hh 信号通过控制核心细胞周期成分对多个器官的细胞周期具有刺激作用。在这里，我们发现 Sonic Hedgehog (Shh) 信号在斑马鱼视网膜中具有相反的作用，导致细胞周期退出，并且这是由细胞周期蛋白激酶抑制剂 p57Kip2 的转录激活介导的。 p57Kip2 活性的丧失与 Shh 突变体的眼睛表型非常相似，并且 p57Kip2 的过度表达可以挽救 Shh 突变体中的细胞周期退出，表明 p57Kip2 对于介导 Shh 诱导的视网膜细胞周期退出是必要且充分的。这些发现提出了一种可能性，即通过调节核心细胞周期成分刺激细胞周期退出可能是 Hh 定向分化所需的一般机制的一部分。
The Hedgehog (Hh) family of signalling proteins control both differentiation and proliferation during animal development. Previous studies have shown that Hh signalling has a stimulatory effect on the cell cycle in several organs by controlling core cell‐cycle components. Here, we show that Sonic hedgehog (Shh) signalling has the opposite effect in the zebrafish retina, where it leads to cell‐cycle exit, and that this is mediated by transcriptional activation of the cyclin kinase inhibitor p57Kip2. The loss of p57Kip2 activity strongly resembles the Shh mutant eye phenotype, and overexpression of p57Kip2 rescues cell‐cycle exit in Shh mutants, indicating that p57Kip2 is both necessary and sufficient to mediate Shh‐induced cell‐cycle exit in the retina. These findings raise the possibility that stimulation of cell‐cycle exit through regulation of core cell‐cycle components may be part of a general mechanism required for Hh‐directed differentiation.