Effect of Apelin receptor signaling on Nodal activity during mesendoderm development

Apelin 受体信号对中内胚层发育过程中 Nodal 活性的影响

• 批准号: RGPIN-2017-06502
• 负责人: Scott, Ian
• 金额: $ 3.64万
• 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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=689921
• 关键词: Effect; Apelin; receptor; signaling; Nodal

The fundamental process in animal development is the miraculous transition of a single cell (the fertilized egg) into the large numbers of diverse cell types that make up our bodies. One of the first steps in this process is the generation of the stem cells that will later make all the cell types of the animal. In the embryo, this process occurs during gastrulation, when there are coordinated cell movements and cell-to-cell communication that generate our body axis and diversify the stem cell populations needed to make the animal. For my research, we study this process using the zebrafish embryo, a fantastic model to examine how early development occurs. Embryos are laid in water, develop rapidly, and are optically clear, allowing us to watch all the cell movements and molecular events that happen during gastrulation and stem cell generation. As we can genetically modify these organisms, we can easily determine how genes regulate this key milestone in animal development.******My lab has found that a cell surface receptor, called the Apelin Receptor (Aplnr), influences development at this key stage. In the absence of the Aplnr function, there is a deficit in formation of the precursors of the heart and digestive organs. Our work has shown that Aplnr acts during gastrulation to boost the activity of the Nodal signaling pathway. This is of great interest, as the levels of Nodal signal a cell receives are known to control what path that cell will follow (heart cell, gut cell, neuron, etc.). Aplnr therefore acts as a dial that fine-tunes how much Nodal signal is active at a key stage in development. This gives us a unique opportunity to study how cells decide to become both the right type and right amount of stem cells to allow animal development to occur.******We now need to understand how the Aplnr influences Nodal signaling. In this research, we will use the zebrafish embryo to determine how Aplnr activity affects early development and production of the various cell types needed in an animal body. Ultimately, this research will provide fundamental information on how the diversity of cell types found in our bodies is generated. Further, our work will help scientists generate specific cell types required for their research, allowing precise modeling of physiology and development.

动物发育的基本过程是单个细胞（受精卵）奇迹般地转变为构成我们身体的大量不同细胞类型。这个过程的第一步是产生干细胞，这些干细胞随后将产生动物的所有细胞类型。在胚胎中，这一过程发生在原肠胚形成期间，此时有协调的细胞运动和细胞间通讯，产生我们的身体轴，并使动物所需的干细胞群多样化。在我的研究中，我们使用斑马鱼胚胎来研究这个过程，这是一个很好的模型来研究早期发育是如何发生的。胚胎被放置在水中，发育迅速，光学清晰，使我们能够观察原肠胚形成和干细胞生成过程中发生的所有细胞运动和分子事件。由于我们可以对这些生物体进行遗传修饰，我们可以很容易地确定基因如何调节动物发育中的这一关键里程碑。我的实验室发现，一种称为Apelin受体（Aplnr）的细胞表面受体在这个关键阶段影响发育。在缺乏Aplnr功能的情况下，心脏和消化器官前体的形成存在缺陷。我们的工作表明，Aplnr在原肠胚形成过程中起作用，以增强Nodal信号通路的活性。这是非常有趣的，因为已知细胞接收的Nodal信号水平控制细胞将遵循的路径（心脏细胞，肠道细胞，神经元等）。因此，Aplnr就像一个表盘，可以在开发的关键阶段微调Nodal信号的活跃程度。这给了我们一个独特的机会来研究细胞如何决定成为正确类型和正确数量的干细胞，以允许动物发育发生。我们现在需要了解Aplnr如何影响Nodal信号。在这项研究中，我们将使用斑马鱼胚胎来确定Aplnr活性如何影响动物体内所需的各种细胞类型的早期发育和生产。最终，这项研究将提供有关我们体内细胞类型多样性如何产生的基本信息。此外，我们的工作将帮助科学家生成他们研究所需的特定细胞类型，从而实现生理学和发育的精确建模。