Molecular and cellular mechanisms of second heart field development in zebrafish.

斑马鱼第二心脏区发育的分子和细胞机制。

• 批准号: 341545-2012
• 负责人: Scott, Ian
• 金额: $ 2.48万
• 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: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572290
• 关键词: Molecular; cellular; mechanisms; second; heart

A fundamental question in biology is how organs develop and assume their mature, adult form. This is especially true for the heart, which must continue to maintain blood flow in the developing embryo while growing and developing. A surprising finding has been that much of heart development occurs by addition of cells to the already beating heart tube. A group of cells termed the "secondary heart field" (SHF) migrates into the heart and forms a large portion of the mature heart, including the right ventricle, outflow tract, much of the atria and septa that separate the 4 chambers. SHF addition occurs in mice, the model typically used to study heart development, at at time when the embryo is developing in the uterus, making detailed observation of this key process very difficult. Due to its optical clarity, rapid external development and amenability to genetic approaches, the zebrafish has become a powerful tool to study how heart development. My group has recently found that development of the zebrafish heart also involves addition of a SHF-like population of cells. As heart development can be visualized in real-time in the zebrafish embryo, we are now positioned to examine the SHF in a way not possible in the mouse model used to date. The experiments outlined in this proposal aim to discover the cellular and molecular mechanisms responsible for SHF development using the many advantages of the zebrafish embryo. Specifically, we will study in real time at the cellular level how SHF cells are added to the developing heart. We will additionally isolate SHF cells at key time points in their development and identify genes that play essential roles in SHF biology. We will therefore be able to examine critical, yet until now impossible to study, aspects of heart development that can only be visualized in a static fashion in other model systems such as the mouse. This will allow us to define key regulators of SHF development and growth of the heart.

生物学中的一个基本问题是器官如何发育并呈现其成熟的成人形式。对于心脏来说尤其如此，它必须在发育中的胚胎中继续维持血液流动，同时生长和发育。一个令人惊讶的发现是，大部分心脏发育是通过向已经跳动的心管添加细胞而发生的。 一组称为“次级心脏区域”（SHF）的细胞迁移到心脏中，并形成成熟心脏的大部分，包括右心室、流出道、大部分心房和分隔4个腔室的隔膜。SHF添加发生在小鼠中，该模型通常用于研究心脏发育，此时胚胎正在子宫中发育，因此很难详细观察这一关键过程。由于其光学清晰，快速的外部发育和遗传方法的顺从性，斑马鱼已成为研究心脏发育的有力工具。我的团队最近发现，斑马鱼心脏的发育也涉及到SHF样细胞群的增加。由于心脏发育可以在斑马鱼胚胎中实时可视化，我们现在可以以迄今为止使用的小鼠模型中不可能的方式检查SHF。 本提案中概述的实验旨在利用斑马鱼胚胎的许多优点来发现SHF发育的细胞和分子机制。具体来说，我们将在细胞水平上真实的时间研究SHF细胞是如何被添加到发育中的心脏中的。我们还将在SHF细胞发育的关键时间点分离SHF细胞，并鉴定在SHF生物学中发挥重要作用的基因。因此，我们将能够检查关键的，但到目前为止还不可能研究，心脏发育的方面，只能在其他模型系统，如小鼠中以静态方式可视化。这将使我们能够定义SHF发育和心脏生长的关键调节因子。