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: $ 11.95万
• 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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=746516
• 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.

发育生物学中的一个主要问题是，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。我们研究被称为外胚层的形态发生运动，它是一片或多层细胞的变薄和铺展。它在动物发育中被广泛使用，包括在人类中，当它出错时，会导致严重的发育模式缺陷。尽管它很重要，但外胚层的细胞和分子基础还没有完全被理解。在这里，我们将重点研究控制外胚化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，斑马鱼是一种重要的脊椎动物模型，在这类研究中具有许多优势。斑马鱼系统为研究细胞行为和基因功能提供了多种方法和实验途径，由于胚胎的透明性，它是分析形态发生的理想工具。此外，斑马鱼胚胎中的外胚层在三个不同的组织环境中平行发生，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调控相互作用。我们的目标是：(1)研究Rab25蛋白的功能，我们已经证明了这是正常的外胚珠所必需的；(2)研究外胚层和细胞团之间关键相互作用的细胞学基础；(3)研究卵黄细胞在外胚层中的作用。通过提供对常见细胞行为的洞察，加深我们对外胚层机制的理解将增强我们对动物发育的一般知识。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个过程，我们最终将能够生成一个模型，说明不同的形态发生机制是如何在生物体水平上进行功能整合的。