Control of cell cycle entry and exiting from the second mitotic wave in the Drosophila developing eye.
Control of cell cycle entry and exiting from the second mitotic wave in the Drosophila developing eye.
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DOI：
10.1186/1471-213x-8-7
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发表时间：
2008-01-24
影响因子：
--
通讯作者：
Du W
中科院分区：
文献类型：
--
作者：
Sukhanova MJ;Du W
在果蝇发育眼的形态发生沟中，所有细胞都停滞在G1期，光感受器细胞开始分化。当细胞离开微丝分裂时，Notch信号是未被承诺的细胞进入被称为“第二有丝分裂波”(SMW)的同步细胞分裂所必需的。SMW中细胞周期的进出是如何调控的，目前尚不清楚。最近的研究表明，Notch信号通过调节Cyclin A和不依赖于Cyclin E的E2F转录因子来控制SMW的S期。我们在这里证明了细胞周期蛋白E依赖的激酶活性是S进入SMW时相所必需的。我们发现，去除Notch信号下游的关键转录因子SU(H)可以阻止SMW中G1/S的转变，并强烈上调Cyclin E/CDK2抑制剂Dacapo(Dap)。我们进一步证明，由bHLH子蛋白(Da)介导的Dap上调对于SMW中SU(H)突变细胞的细胞周期停滞是重要的。最后，我们发现去除DAP会导致果蝇发育中眼睛中额外的细胞增殖和非光感受器细胞的积累。我们的数据表明，在SMW的S期，Cyclin E/CDK2激酶的活性是绝对必需的，而DAP是离开SMW的细胞正确停止细胞周期所必需的。此外，我们的结果表明，SMW中Noch和SU(H)突变细胞的G1期停滞是由不同的机制调节的，Dap的上调有助于SU(H)突变细胞的G1期停滞。
In the morphogenetic furrow (MF) of the Drosophila developing eye, all cells arrest in G1 and photoreceptor cell differentiation initiates. As the cells exit the MF, Notch signaling is required for the uncommitted cells to enter a synchronous round of cell division referred to as the "second mitotic wave" (SMW). How cell cycle entry and exit in SMW is regulated remains unclear. Recent studies have suggested that Notch signaling controls S phase in the SMW by regulating Cyclin A and the E2F transcription factor independent of Cyclin E. In this manuscript, we investigate the developmental regulation of cell cycle entry into and exit from SMW. We demonstrate here that Cyclin E-dependent kinase activity is required for S phase entry in SMW. We show that removal of Su(H), a key transcription factor downstream of Notch signaling, blocks G1/S transition in SMW with strong upregulation of the Cyclin E/Cdk2 inhibitor Dacapo (Dap). We further show that the upregulation of Dap, which is mediated by bHLH protein Daughterless (Da), is important for cell cycle arrest of Su(H) mutant cells in SMW. Finally we show that removal of Dap leads to additional cell proliferation and an accumulation of the non-photoreceptor cells in the Drosophila developing eye. Our data demonstrate that Cyclin E/Cdk2 kinase activity is absolutely required for S phase in SMW, and that Dap is required for the proper cell cycle arrest of cells exiting the SMW. In addition, our results suggest that the G1 arrest of notch and Su(H) mutant cells in the SMW are regulated by distinct mechanisms, and that the upregulation of Dap contributes the G1 arrest of Su(H) mutant cells.