Time-keeping mechanisms of embryonic cell cycles

胚胎细胞周期的计时机制

基本信息

批准号：
10603282
负责人：
Stefano Di Talia
金额：
$ 34.23万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10603282
关键词：
Actomyosin Address Affect Biochemical Blastoderm Body part Cell Cycle Cell Cycle Regulation Cell Differentiation process Cell Nucleus Cell Proliferation Cell Proliferation Regulation Cell division Cell model Cell physiology Cells Chemicals Chromosome abnormality Computing Methodologies Cytoplasm Cytoskeleton DNA biosynthesis Development Disease Dorsal Drosophila genus Embryo Embryology Embryonic Development Ensure Feedback Gene Expression Genes Genetic Transcription Genome Genomic Instability Goals Histones Image Link Malignant Neoplasms Mechanics Messenger RNA Methods Microtubules Mitosis Mitotic Molecular Genetics Morphogenesis Nuclear Organism Outcome Pattern Play Positioning Attribute Process Regulation Resolution Role Side Signal Transduction System Testing Time Tissues Transcriptional Regulation Work embryo cell experimental study gastrulation gene network imaging approach imaging modality improved in vivo inhibitor insight interdisciplinary approach mechanical signal migration morphogens novel quantitative imaging spatiotemporal

项目摘要

ABSTRACT During embryonic development each body part is programmed to contain an accurate number and arrangement of cells. This accuracy is achieved through precise regulation of cell proliferation. The overarching goal of this proposal is to reveal the mechanisms that ensure accurate control of the cell cycle during Drosophila embryonic development. We will study three fundamental questions of cell cycle regulation in morphogenesis by addressing the following Aims. In Aim 1, we will study how the interplay of biochemical and mechanical signals ensures accurate nuclear positioning. Specifically, we will address how the activity of the cell cycle oscillator and microtubule cytoskeleton are integrated to control nuclear migration to the embryo cortex. In Aim 2, we will study how the nuclear-to-cytoplasmic ratio controls the cell cycle via the activation of the DNA replication checkpoint and zygotic genome activation. We will also investigate the feedback mechanisms by which the cell cycle and zygotic expression influence each other and ensure a robust maternal-to-zygotic transition. In Aim 3, we will elucidate how transcriptional regulation of cdc25string ensures precise regulation of the timing of mitosis during gastrulation. We will also investigate the mechanisms controlling mitotic domains on the dorsal side of the embryos, where they are directly linked to the dynamic of the Decapentaplegic (Dpp) morphogen gradients. Collectively, our experiments will define a quantitative framework elucidating how the cell cycle is regulated accurately during embryonic development.

抽象的在胚胎开发过程中，每个身体部位都被编程为包含一个准确的数字和布置细胞。通过精确调节细胞增殖来实现这种准确性。总体目标建议是揭示确保果蝇胚胎中细胞周期准确控制细胞周期的机制发展。我们将通过解决形态发生中细胞周期调节的三个基本问题以下目标。在AIM 1中，我们将研究生化和机械信号的相互作用如何确保准确的核定位。具体而言，我们将解决细胞周期振荡器的活动和微管细胞骨架被整合以控制核迁移到胚胎皮质。在AIM 2中，我们将学习核与胞质比如何通过DNA复制检查点的激活来控制细胞周期和合子基因组激活。我们还将调查细胞周期和细胞周期的反馈机制合子表达相互影响，并确保良好的母体到杂种过渡。在AIM 3中，我们将阐明CDC25STRING的转录调节如何确保对有丝分裂时间的精确调节胃。我们还将研究控制有丝分裂域的机制胚胎，它们直接与脱皮颌（DPP）形态梯度的动态联系在一起。总的来说，我们的实验将定义一个定量框架，以阐明细胞周期的调节方式在胚胎发育过程中准确。

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）

Waves in Embryonic Development.

DOI：
10.1146/annurev-biophys-111521-102500
发表时间：
2022-05-09
期刊：
ANNUAL REVIEW OF BIOPHYSICS
影响因子：
12.4
作者：
Di Talia, Stefano;Vergassola, Massimo
通讯作者：
Vergassola, Massimo

Temperature-Induced uncoupling of cell cycle regulators.

DOI：
10.1016/j.ydbio.2020.11.010
发表时间：
2021-03
期刊：
Developmental biology
影响因子：
2.7
作者：
Falahati H;Hur W;Di Talia S;Wieschaus E
通讯作者：
Wieschaus E

Manipulating the nature of embryonic mitotic waves.

DOI：
10.1016/j.cub.2022.10.014
发表时间：
2022-11-21
期刊：
CURRENT BIOLOGY
影响因子：
9.2
作者：
Hayden, Luke;Hur, Woonyung;Vergassola, Massimo;Di Talia, Stefano
通讯作者：
Di Talia, Stefano

Cullin-5 mutants reveal collective sensing of the nucleocytoplasmic ratio in Drosophila embryogenesis.

DOI：
10.1016/j.cub.2022.03.007
发表时间：
2022-05-09
期刊：
CURRENT BIOLOGY
影响因子：
9.2
作者：
Hayden, Luke;Chao, Anna;Deneke, Victoria E.;Vergassola, Massimo;Puliafito, Alberto;Di Talia, Stefano
通讯作者：
Di Talia, Stefano

Chemical waves in cell and developmental biology.