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Mechanisms and developmental functions of cytoplasmic flows in early embryogenesis

早期胚胎发生中细胞质流动的机制和发育功能

基本信息

批准号：
10297436
负责人：
Stefano Di Talia
金额：
$ 30.13万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-20 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10297436
关键词：
Actomyosin Address Affect Anterior Apical Biochemical Biological Biological Process Biophysics Blastoderm CDC2 gene Cell Cycle Cell Cycle Regulation Cell Nucleus Cells Characteristics Chemical Models Complex Computing Methodologies Coupling Cullin 5 Protein Cytoplasm Cytoplasmic streaming Cytoskeleton Cytosol Data Development Diffusion Drosophila genus Embryo Embryonic Development Ensure Epithelial Event Feedback Fertilization Gel Generations Genes Genetic Genetic Diseases Geometry Giant Cells Goals Human Lead Link Liquid substance Location Mammals Measures Mechanics Methodology Methods Mitotic Modeling Molecular Morphogenesis Nature Normal Cell Nuclear Outcome Pattern Play Positioning Attribute Process Property Protein phosphatase Proteins Role Signal Transduction System Temperature Testing Time Tissues Transgenic Organisms Work biological systems biophysical model blastomere structure constriction experimental study in vivo insight mathematical model morphogens mutant novel optogenetics organ growth physical process physical property programs quantitative imaging spatiotemporal ubiquitin ligase

项目摘要

Abstract The integration of biochemical and mechanical signals is an important and ubiquitous feature of biological systems. During embryonic development, this integration is required for complex tissue organization and function. We have recently shown that during the early, pre-blastoderm stages of Drosophila embryogenesis the integrated activities of the cell cycle oscillator and actomyosin contractility generate a self-organized mechanism of nuclear positioning which is essential for synchronization of the cell cycle. At the core of this mechanism are cytoplasmic flows that are initiated by cortical contractions. These, in turn, are linked spatiotemporally to the oscillation of mitotic Cyclin-dependent kinase 1 (Cdk1) and protein phosphatase 1 (PP1). These flows are able to transport nuclei and are responsible for their accurate positioning across the embryo. The goal of this proposal is to build on these novel findings and to understand more deeply the mechanisms and developmental functions of cytoplasmic flows. We will take three approaches to address these fundamental questions. 1. We will build a biophysical model that captures the coupling of biochemical and mechanical signals and the effective physical properties of the cytoplasm. The coupling between the cytoskeleton and the cytosol will be modeled by a two- fluid model: an active contractile gel and a viscous cytosol. 2. We will use genetic and optogenetics approaches to alter cortical contractility as well as transgenic approaches to change the geometry of the embryo and a novel setup to control temperature. These experiments will provide a novel paradigm for understanding the molecular mechanisms underlying the generation and the properties of cytoplasmic flows. 3. We will test whether cytoplasmic flows play a role in the formation of morphogen gradients. Specifically, we will use quantitative imaging and mathematical modeling to determine whether cytoplasmic flows affect the formation of the anterior- posterior gradient of Bicoid morphogen in the syncytial Drosophila embryo. Taken together these studies will provide a new paradigm for the integration of biochemical and mechanical signals that is likely to have general relevance for other developmental systems.

摘要生物化学和机械信号的整合是生物学的一个重要和普遍存在的特征，在胚胎发育期间，这种整合对于复杂的组织组织和我们最近的研究表明，在果蝇胚胎发生的早期，前胚盘阶段，细胞周期振荡器和肌动球蛋白收缩性的综合活动产生了一种自组织机制细胞核定位是细胞周期同步化的关键。这种机制的核心是这些细胞质流动是由皮层收缩启动的。这些，反过来，在时空上连接到有丝分裂细胞周期蛋白依赖性激酶1（Cdk 1）和蛋白磷酸酶1（PP 1）的振荡。运输细胞核，并负责它们在胚胎中的准确定位。是建立在这些新发现的基础上，更深入地了解细胞质流动。我们将采取三种方法来解决这些基本问题。1.我们将建立一个生物物理模型，该模型捕获生物化学和机械信号的耦合以及有效的物理特性。细胞质的性质。细胞骨架和胞质溶胶之间的耦合将由一个双链模型来模拟。流体模型：一个主动收缩的凝胶和一个粘性的胞质溶胶。2.我们将使用遗传学和光遗传学的方法改变皮层收缩性以及转基因方法改变胚胎的几何形状，这些实验将提供一个新的范例，了解分子细胞质流的产生和性质的机制。3.我们将测试是否细胞质流动在形态梯度的形成中起作用。具体来说，我们将使用定量的成像和数学建模，以确定细胞质流动是否影响前额叶的形成后梯度的Bicoid形态发生在合胞体果蝇胚胎。综合这些研究将提供了一个新的模式，为一体化的生化和机械信号，很可能有一般与其他发展体系的关系。