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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：
10491186
负责人：
Stefano Di Talia
金额：
$ 28.89万
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/10491186
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 mechanical signal 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：生物化学和生物机械信号的有机结合是现代生物科学的重要组成部分和普遍存在的特征。系统。在胚胎组织的发展过程中，对于复杂的组织和组织结构来说，这种组织集成是必要的。功能。我们最近发现，在果蝇的早期，前胚层和胚胎发生的各个阶段都是如此。整合的活动包括细胞周期、振荡器和肌动球蛋白的收缩能力，以产生一个完整的自组织调控机制。对于整个细胞周期的同步进程来说，核子定位是至关重要的。尤其是这个核子机制的核心是什么。细胞质的流动表明，这些细胞并不是由大脑皮层的收缩启动的，而这些又反过来又与这些细胞在时空上的联系在一起。有丝分裂周期蛋白依赖性蛋白激酶1(CDK1)和蛋白磷酸酶1(PP1)的振荡信号。这些信号传导是可能的。为了更好地运输核，他们要为他们在整个胚胎中更准确的定位方案负责。这是这项新提案的主要目标。我们希望在这些新颖的研究成果的基础上再接再厉，更深入地了解这些新的发展机制和发展机制的功能。我们将采取三种基本方法来解决这些根本的问题。1.我们将不会建立一个新的体系。生物物理学模型认为，它捕捉了生化信号和机械信号之间的相互耦合关系，并提供了最有效的物理信号。细胞质的性质。细胞骨架和细胞质之间的偶联关系将不会由一个新的二元组来模拟。流体模型：一种非常活跃的收缩凝胶，一种非常粘稠的细胞质。2.我们将继续使用遗传学和光遗传学的方法。为了改变大脑皮质的收缩能力，以及转基因技术的方法，我们需要改变人类胚胎的几何形状，并创造一种全新的小说。建立控制温度的装置。这些实验将为我们理解生物分子提供一种全新的实验范式。机制是下一代的基础，并决定了细胞质流动的基本性质。3.我们将不会测试是否存在。细胞质的流动将在形态原和梯度的形成过程中发挥重要作用。具体地说，我们将不使用定量的方法。成像技术和数学模型有助于确定细胞质血流是否会影响前牙本质的形成。在果蝇的合胞体胚胎中，类双胞体和形态原的后部梯度分布。将这些研究结合在一起，将是未来的研究方向。提供了一种全新的技术范式，用于实现生物化学技术和机械技术信号的有机集成，这是一种很可能无法实现的通用技术。这与其他可持续发展的技术系统具有相关性。