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

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

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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.

抽象的生化和机械信号的整合是生物学的重要且无处不在的特征系统。在胚胎开发过程中，复杂的组织组织和功能。我们最近表明，在果蝇胚胎发生的早期，前芽剂前阶段细胞周期振荡器和肌动球蛋白收缩力的综合活性产生自组织的机制核位置，这对于细胞周期同步至关重要。这种机制的核心是由皮质收缩引发的细胞质流。这些反过有丝分裂细胞周期蛋白依赖性激酶1（CDK1）和蛋白质磷酸酶1（PP1）的振荡。这些流动区域运输核并负责在整个胚胎上的准确定位。该提议的目标是基于这些新颖的发现，并更深入地了解机制和发展功能细胞质流。我们将采用三种方法来解决这些基本问题。 1。我们将建造一个捕获生化和机械信号的耦合以及有效物理的生物物理模型细胞质的特性。细胞骨架和细胞质之间的耦合将由两种流体模型：活性收缩凝胶和粘性细胞质。 2。我们将使用遗传和光遗传学方法改变皮质收缩力以及转基因方法，以改变胚胎的几何形状和新颖设置以控制时间正性。这些实验将为理解分子提供新的范式产生的机制和细胞质流的特性。 3。我们将测试是否细胞质流动在形成梯度的形成中起作用。具体来说，我们将使用定量成像和数学建模，以确定胞质流是否影响前质流的形成果蝇胚胎中生物形态形态学的后置梯度。总之这些研究将为整合生化和机械信号的整合提供了新的范式与其他发展系统相关。