CELL CYCLE CHECKPOINTS IN THE XENOPUS EMBRYO

非洲爪蟾胚胎中的细胞周期检查点

基本信息

批准号：
6636325
负责人：
JILL C SIBLE
金额：
$ 28.55万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-05-01 至 2006-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6636325
关键词：
Xenopus Xenopus oocyte apoptosis biological signal transduction cell cycle cell growth regulation developmental genetics early embryonic stage embryogenesis vertebrate embryology

项目摘要

Checkpoints in the eukaryotic cell cycle maintain the integrity of the genome by arresting the cell cycle when DNA is damaged or incompletely replicated. Checkpoint pathways converge upon the activities of cyclin-dependent kinases (Cdks), enzymes that catalyze cell cycle progression. Early embryonic cell cycles of the frog Xenopus laevis provide rare examples of non-pathological cell divisions that lack checkpoints. Following fertilization, the Xenopus egg begins twelve rapid and synchronous cell cycles that oscillate between DNA replication and mitosis without growth, gap phases, or checkpoints. These early cell cycles proceed "unchecked" when DNA is damaged or DNA replication is blocked. Completion of the twelfth cleavage marks the midblastula transition (MBT). At the MBT, embryonic gene expression begins, and the cell cycle remodels, lengthening as it acquires the gap phases and checkpoints of a typical adult cell cycle. The proposed project will investigate the role of XChk1 during embryogenesis of Xenopus. XChk1 is homologous to mammalian and yeast Chk1, which inactivate Cdks to maintain cell cycle arrest. XChk1 is also homologous to Grp1, which functions in timing the MBT during Drosophila development. XChk1 function will be investigated during the remodeling cell cycles of the Xenopus embryo. Specific aims are to investigate 1) when XChk1 signaling becomes operational, 2) the requirement for XChk1 in DNA damage and DNA replication checkpoints, and 3) the relationship between XChk1 and a developmental program of apoptosis, 4) the role of XChk1 in timing the MBT, and 5) the targets of XChk1 signaling. The embryonic cell divisions of Xenopus, which remodel from rapid to regulated cell cycles, provide a uniquely rich system in which to investigate the engagement of checkpoints. A better understanding of the signaling pathways that mediate cell cycle checkpoints during frog embryogenesis may help us to modulate other atypical cell cycles. These include the exuberant cell cycles of cancer, the failing cell cycles of aging and senescence, and the usurped cell cycles of infectious disease.

当 DNA 受损或复制不完全时，真核细胞周期中的检查点通过阻止细胞周期来维持基因组的完整性。检查点通路集中在细胞周期蛋白依赖性激酶 (Cdks) 的活性上，这些酶是催化细胞周期进程的酶。非洲爪蟾的早期胚胎细胞周期提供了缺乏检查点的非病理性细胞分裂的罕见例子。受精后，非洲爪蟾卵开始 12 个快速同步的细胞周期，在 DNA 复制和有丝分裂之间振荡，没有生长、间隙期或检查点。当 DNA 受损或 DNA 复制受阻时，这些早期细胞周期就会“不受控制”地进行。第十二次卵裂的完成标志着囊胚中转变（MBT）。在MBT，胚胎基因开始表达，细胞周期进行重塑，并随着获得典型成体细胞周期的间隙期和检查点而延长。拟议的项目将研究 XChk1 在非洲爪蟾胚胎发生过程中的作用。 XChk1 与哺乳动物和酵母 Chk1 同源，后者使 Cdks 失活以维持细胞周期停滞。 XChk1 也与 Grp1 同源，Grp1 在果蝇发育过程中负责调节 MBT 时间。 XChk1 功能将在爪蟾胚胎重塑细胞周期期间进行研究。具体目标是研究 1) XChk1 信号传导何时发挥作用，2) DNA 损伤和 DNA 复制检查点对 XChk1 的需求，以及 3) XChk1 与细胞凋亡发育程序之间的关系，4) XChk1 在计时细胞凋亡中的作用MBT，以及 5) XChk1 信号传导的目标。非洲爪蟾的胚胎细胞分裂从快速细胞周期重塑为调节细胞周期，为研究检查点的参与提供了一个独特的丰富系统。更好地了解青蛙胚胎发生过程中介导细胞周期检查点的信号通路可能有助于我们调节其他非典型细胞周期。这些包括癌症的旺盛细胞周期、衰老和衰老的衰退细胞周期以及传染病的篡夺细胞周期。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Altered expression of Chk1 disrupts cell cycle remodeling at the midblastula transition in Xenopus laevis embryos.

Chk1 表达的改变会破坏非洲爪蟾胚胎中囊胚转变时的细胞周期重塑。

DOI：
发表时间：
2004-02
期刊：
影响因子：
0
作者：
Petrus, Matthew J;Wilhelm, Dayna E;Murakami, Monica;Kappas, Nicholas C;Carter, Ayesha D;Wroble, Brian N;Sible, Jill C
通讯作者：
Sible, Jill C

Near-infrared laser delivery of nanoparticles to developing embryos: a study of efficacy and viability.

近红外激光将纳米颗粒递送至发育中的胚胎：功效和活力的研究。

DOI：
发表时间：
2011-05
期刊：
影响因子：
4.7
作者：
Umanzor;Wade, Emily C;Gifford, Aliya;Nontapot, Kankowan;Cruz;Gotoh, Tetsuya;Sible, Jill C;Khodaparast, Giti A
通讯作者：
Khodaparast, Giti A

Modeling regulatory networks at Virginia Tech.

弗吉尼亚理工大学的监管网络建模。

DOI：
发表时间：
2003
期刊：
影响因子：
0
作者：
Allen, Nicholas A;Calzone, Laurence;Chen, Katherine C;Ciliberto, Andrea;Ramakrishnan, Naren;Shaffer, Clifford A;Sible, Jill C;Tyson, John J;Vass, Marc T;Watson, Layne T;Zwolak, Jason W
通讯作者：
Zwolak, Jason W

Wee1 kinase alters cyclin E/Cdk2 and promotes apoptosis during the early embryonic development of Xenopus laevis.

Wee1 激酶改变细胞周期蛋白 E/Cdk2 并促进非洲爪蟾早期胚胎发育过程中的细胞凋亡。