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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

基本信息

批准号：
10285981
负责人：
Rocky Diegmiller
金额：
$ 3.32万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2022-05-31
项目状态：
已结题

项目摘要

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.

项目摘要在许多研究过的动物物种中，包括哺乳动物，未来的卵母细胞在一群细胞中发育，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动力学沟。虽然这种有趣的多细胞生物的形成和结构系统已被广泛研究，其动力学知之甚少，留下了许多关键问题，卵母细胞的决定和发育尚未解决。我将在果蝇中研究其中的两个问题，该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。通过实验、建模和计算方法，我将研究生殖系中的一个细胞如何选择细胞簇作为未来的卵母细胞，以及包含卵母细胞的生殖系细胞簇和营养细胞在发育过程中生长。具体而言，目标1旨在评估差异卵母细胞决定的预模式化和自组织机制的贡献。专注于融合体，一种在卵子发生早期细胞间通讯所必需的膜结构，最近发现的涉及mRNA定位和翻译的正反馈回路，我将建立数据- 用于卵母细胞选择的数学模型。同时，目标2将研究卵母细胞的生长，支持细胞，使用生殖细胞群作为一个易于处理的系统，探索缩放定律如何当细胞一起生长时，单细胞生长研究所建立的基因改变了。特别是，我将重点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加的细胞生殖系细胞簇内的体积。这些拟议的研究得到了以下方面的支持：强大的初步结果，包括用于3D图像重建的机器学习方法，形态测量分析，应该提供新的见解，一些动物卵子发生的第一步。