Zebrafish epiboly as a model of vertebrate embryonic cell rearrangement

斑马鱼表皮作为脊椎动物胚胎细胞重排的模型

• 批准号: RGPIN-2018-04862
• 负责人: Bruce, Ashley
• 金额: $ 5.97万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=713229
• 关键词: Zebrafish; epiboly; model; vertebrate; embryonic

A major question in developmental biology is how morphogenesis, or the coordination of cell shape and cell movement, generates the correct structure of tissues and organs in all animals. We study the morphogenetic movement called epiboly which is the thinning and spreading of a sheet or multi-layer of cells. It is used widely in animal development, including in humans, and when it goes wrong, profound developmental patterning defects result. Despite its importance, the cellular and molecular basis of epiboly is not fully understood. Here we focus on the molecular and cellular mechanisms that control the process of epiboly in order to generate the adult vertebrate body plan. This work will be conducted using the zebrafish embryo, an important vertebrate model with many advantages for this type of research. The zebrafish system provides a variety of methodologies and experimental approaches to study cell behavior and gene function, and it is ideal for analyzing morphogenesis due to the transparency of the embryo. In addition, epiboly in the zebrafish embryo occurs in parallel in three distinct tissue contexts, allowing us to study it in a cell sheet, a cell mass and a yolk cell; and to analyze the mechanical and regulatory interactions between these regions. Our objectives are to: (1) investigate the function of the Rab25 protein, which we have shown is required for normal epiboly (2) investigate the cellular basis of critical interactions between the cell sheet and the cell mass during epiboly and (3) investigate the role of the yolk cell in epiboly. Deepening our understanding of the mechanisms of epiboly will enhance our knowledge of animal development in general by providing insights into common cell behaviors. Importantly, by using the zebrafish model to study the same overall process in three mechanistically distinct tissue contexts, we will be able to ultimately generate a model of how distinct morphogenetic mechanisms are functionally integrated at the organismal level.

发育生物学的一个主要问题是形态发生，或细胞形状和细胞运动的协调，如何在所有动物中产生正确的组织和器官结构。我们研究称为外延的形态发生运动，它是一层或多层细胞的变薄和扩散。它广泛应用于动物发育，包括人类，当它出错时，就会导致严重的发育模式缺陷。尽管它很重要，但外泌体的细胞和分子基础尚未完全了解。在这里，我们重点关注控制脱落过程的分子和细胞机制，以生成成年脊椎动物的身体计划。 这项工作将使用斑马鱼胚胎进行，斑马鱼胚胎是一种重要的脊椎动物模型，对于此类研究具有许多优势。斑马鱼系统提供了多种方法和实验方法来研究细胞行为和基因功能，由于胚胎的透明性，它非常适合分析形态发生。此外，斑马鱼胚胎中的表皮脱落在三种不同的组织环境中并行发生，使我们能够在细胞片、细胞团和卵黄细胞中研究它；并分析这些区域之间的机械和监管相互作用。我们的目标是：(1) 研究 Rab25 蛋白的功能，我们已证明该蛋白是正常脱落所需的 (2) 研究脱落过程中细胞片层和细胞团之间关键相互作用的细胞基础，以及 (3) 研究卵黄细胞在脱落中的作用。 加深我们对脱落机制的理解，将通过提供对常见细胞行为的见解来增强我们对动物发育的总体了解。重要的是，通过使用斑马鱼模型在三个机械上不同的组织环境中研究相同的整体过程，我们将能够最终生成一个模型，说明不同的形态发生机制如何在有机体水平上进行功能整合。