CELL CYCLE CHECKPOINTS IN THE XENOPUS EMBRYO

非洲爪蟾胚胎中的细胞周期检查点

• 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
• 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

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.

真核细胞周期中的检查点通过阻止DNA受损或复制不完全时的细胞周期来维持基因组的完整性。检查点途径集中于周期蛋白依赖激酶（Cdks）的活性，这些酶催化细胞周期进程。非洲爪蟾的早期胚胎细胞周期提供了罕见的缺乏检查点的非病理性细胞分裂的例子。受精后，爪蟾卵开始12个快速和同步的细胞周期，在DNA复制和有丝分裂之间振荡，没有生长、间隙期或检查站。当DNA受损或DNA复制受阻时，这些早期细胞周期“不受控制”地进行。第十二道卵裂的完成标志着中囊胚过渡（MBT）。在MBT，胚胎基因表达开始，细胞周期重塑，随着它获得典型成人细胞周期的间隙期和检查点而延长。拟建项目将研究XChk1在爪蟾胚胎发生过程中的作用。XChk1与哺乳动物和酵母的Chk1同源，其灭活Cdks以维持细胞周期阻滞。XChk1也与Grp1同源，Grp1在果蝇发育过程中起调控MBT的作用。XChk1的功能将在爪蟾胚胎重塑细胞周期中进行研究。具体目的是研究1)XChk1信号何时开始运作，2)DNA损伤和DNA复制检查点对XChk1的需求，3)XChk1与细胞凋亡发育程序之间的关系，4)XChk1在MBT定时中的作用，以及5)XChk1信号的靶标。非洲爪蟾的胚胎细胞分裂，从快速细胞周期到调节细胞周期的转变，为研究检查点的参与提供了一个独特的丰富系统。更好地理解在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，衰老和衰老的衰竭细胞周期，以及传染病的篡夺细胞周期。

项目成果

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。

• 发表时间: 2004
• 期刊: Cell cycle (Georgetown, Tex.)
• 作者: Petrus,MatthewJ;Wilhelm,DaynaE;Murakami,Monica;Kappas,NicholasC;Carter,AyeshaD;Wroble,BrianN;Sible,JillC
• 通讯作者: Sible,JillC

Chk2/Cds1 protein kinase blocks apoptosis during early development of Xenopus laevis.

Chk2/Cds1 蛋白激酶可阻断非洲爪蟾早期发育过程中的细胞凋亡。

• DOI: 10.1002/dvdy.20449
• 发表时间: 2005
• 期刊: Developmental dynamics : an official publication of the American Association of Anatomists.
• 作者: Wroble,BrianN;Sible,JillC
• 通讯作者: Sible,JillC

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

• DOI: 10.1002/biot.201000205
• 发表时间: 2011-05
• 期刊: BIOTECHNOLOGY JOURNAL
• 影响因子: 4.7
• 作者: Umanzor-Alvarez, Jose;Wade, Emily C.;Gifford, Aliya;Nontapot, Kankowan;Cruz-Reese, Ariana;Gotoh, Tetsuya;Sible, Jill C.;Khodaparast, Giti A.
• 通讯作者: Khodaparast, Giti A.

Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse.

• DOI: 10.1016/j.ydbio.2015.09.023
• 发表时间: 2016-01-15
• 期刊: Developmental biology
• 影响因子: 2.7
• 作者: Schill EM;Lake JI;Tusheva OA;Nagy N;Bery SK;Foster L;Avetisyan M;Johnson SL;Stenson WF;Goldstein AM;Heuckeroth RO
• 通讯作者: Heuckeroth RO

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

WEE1激酶会改变细胞周期蛋白E/CDK2，并在Xenopus laevis的早期胚胎发育期间促进细胞凋亡。

• DOI: 10.1186/1471-213x-7-119
• 发表时间: 2007-10-25
• 期刊: BMC developmental biology
• 作者: Wroble BN;Finkielstein CV;Sible JC
• 通讯作者: Sible JC