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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=664608
• 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)奇迹般地转变为组成我们身体的大量不同类型的细胞。这一过程的第一步是产生干细胞，这些干细胞将在以后形成动物的所有细胞类型。在胚胎中，这一过程发生在原肠形成期间，这时有协调的细胞运动和细胞间的通讯，产生我们的体轴，并使制造动物所需的干细胞种群多样化。在我的研究中，我们使用斑马鱼胚胎来研究这一过程，这是一个检验早期发育如何发生的奇妙模型。胚胎在水中孵化，发育迅速，光学透明，使我们能够观察原肠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进行基因改造，我们可以很容易地确定基因如何调控动物发育的这一关键里程碑。*我的实验室发现，一种名为Apelin受体(Aplnr)的细胞表面受体影响着这一关键阶段的发育。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在原肠形成过程中起作用，促进Nodal信号通路的活性。这是非常有趣的，因为细胞接收到的结节信号的水平是已知的，控制细胞将沿着什么路径走(心脏细胞、肠道细胞、神经元等)。因此，Aplnr充当一个刻度盘，微调在发育的关键阶段有多少Nodal信号活跃。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适当数量的干细胞，以使动物发育。*我们现在需要了解Aplnr是如何影响Nodal信号的。在这项研究中，我们将使用斑马鱼胚胎来确定Aplnr活性如何影响动物身体所需的各种细胞类型的早期发育和生产。最终，这项研究将提供关于我们身体中发现的细胞类型多样性是如何产生的基本信息。此外，我们的工作将帮助科学家产生他们的研究所需的特定细胞类型，从而能够对生理和发育进行精确的建模。