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.

项目概要 在许多研究的动物物种中，包括哺乳动物，未来的卵母细胞在一群细胞内发育，这些细胞 通过细胞质桥网络交换分子和细胞器，这些细胞质桥由稳定的 和增强的细胞因子皱纹。虽然这一类有趣的多细胞生物的形成和结构 系统已被广泛研究，但对其动力学知之甚少，留下了许多关键问题 卵母细胞的确定和发育尚未得到解答。我将在果蝇中研究其中两个问题， 实验模型继续为动物卵子发生的一般机制提供有价值的见解。 使用实验、建模和计算方法，我将研究生殖系中的一个细胞如何 细胞簇被选为未来的卵母细胞，以及生殖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。具体来说，目标 1 旨在评估差异 卵母细胞决定的预模式和自组织机制的贡献。专注于 纺锤体是一种膜结构，对于早期卵子发生过程中的细胞间通讯至关重要 最近发现了一个涉及 mRNA 定位和翻译的正反馈循环，我将建立数据- 卵母细胞选择的驱动数学模型。与此同时，目标 2 将研究卵母细胞的生长和 支持细胞，使用种系簇作为一个易于处理的系统来探索缩放法则 当细胞一起生长时，单细胞生长的研究会改变。我特别会重点 研究细胞核和核仁的大小调节，旨在了解它们的大小如何适应快速增长的细胞 生殖细胞簇内的体积。这些拟议研究的完成得到了以下机构的支持 强有力的初步结果，包括用于 3D 图像重建的机器学习方法和 形态测量分析应该为动物卵子发生的一些第一步提供新的见解。