Symmetry Breaking and Collective Cell Growth in Drosophila Oogenesis

果蝇卵子发生中的对称性破缺和集体细胞生长

• 批准号: 9910741
• 负责人: Rocky Diegmiller
• 金额: $ 3.91万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9910741
• 关键词: Address; Animal Model; Animals; Cell Nucleus; Cell Volumes; Cells; Computational Technique; Consumption; Cyst; Data; Data Set; Development; Drosophila genus; Experimental Models; Feedback; Female; Future; Genetic Techniques; Growth; Image; Imaging Techniques; Insecta; Laws; Machine Learning; Mammals; Manuals; Messenger RNA; Nurses; Oocytes; Oogenesis; Organelles; Organism; Regulation; Regulation of Cell Size; Statistical Data Interpretation; Structure; Study models; Supporting Cell; System; Testing; Three-Dimensional Image; Three-Dimensional Imaging; Time; Translations; Work; base; cell growth; design; egg; experimental study; image reconstruction; imaging study; improved; insight; intercellular communication; mathematical model; quantitative imaging; reconstruction; supervised learning; tool

PROJECT SUMMARY In many studied animal species, including mammals, the future oocyte develops within a cluster of cells that exchange molecules and organelles through a network of cytoplasmic bridges, which are formed by stabilized and reinforced cytokinetic furrows. While the formation and structure of this interesting class of multicellular systems has been extensively studied, their dynamics is poorly understood, leaving many critical questions about oocyte determination and development unanswered. I will investigate two of these questions in Drosophila, an experimental model that continues to provide valuable insights into general mechanisms of animal oogenesis. Using experimental, modeling, and computational approaches, I will investigate how one cell within the germline cell cluster is chosen to be the future oocyte and how the germline cell cluster comprising the oocyte and supporting nurse cells grows during development. Specifically, Aim 1 is designed to evaluate the differential contributions of the prepatterning and self-organizing mechanisms of oocyte determination. Focusing on the fusome, a membranous structure that is essential for intercellular communication in early oogenesis, and on a recently discovered positive feedback loop involving mRNA localization and translation, I will establish data- driven mathematical models for oocyte selection. In parallel, Aim 2 will investigate growth of the oocyte and supporting cells, using the germline cluster as a tractable system for exploring how the scaling laws established by studies of single cell growth are altered when cells grow together. In particular, I will focus on size regulation of nuclei and nucleoli, aiming to understand how their sizes adjust to rapidly increasing cell volumes within the germline cell cluster. The completion of these proposed studies, which are supported by strong preliminary results, including a machine learning approach for 3D image reconstructions and morphometric analysis, should provide new insights into some of the first steps of animal oogenesis.

项目摘要 在包括哺乳动物在内的许多研究的动物物种中，未来的卵母细胞在一群细胞内发展， 通过细胞质桥网络交换分子和细胞器，由稳定形成 并加强细胞力学沟。而这种有趣类的多细胞的形成和结构 系统已经进行了广泛的研究，他们的动态知识很少，留下了许多关键问题 卵母细胞的确定和发育未得到答复。我将在果蝇中调查其中两个问题，一个 实验模型继续为动物卵子发生的一般机制提供宝贵的见解。 使用实验，建模和计算方法，我将研究种系中的一个细胞 选择细胞簇是未来的卵母细胞，以及种系细胞簇如何包含卵母细胞和 支持护士细胞在发育过程中生长。具体而言，AIM 1旨在评估差异 卵母细胞确定的预培养和自组织机制的贡献。专注于 Fusome，一种膜结构，对于早期卵子发生的细胞间通信至关重要， 最近发现的涉及mRNA定位和翻译的正面反馈回路，我将建立数据 - 用于选择卵母细胞的驱动数学模型。同时，AIM 2将研究卵母细胞的生长和 支持细胞，使用种系簇作为探索缩放定律的可寓言系统 通过对单个细胞生长的研究确定，当细胞一起生长时会改变。特别是，我将集中精力 关于核和核仁的大小调节，旨在了解它们的尺寸如何适应迅速增加的细胞 种系细胞簇中的体积。这些提出的研究的完成，由 强大的初步结果，包括用于3D图像重建的机器学习方法和 形态分析应为动物卵子发生的第一步提供新的见解。