Functional RNAs in Axis Formation

该计划旨在了解一个非常基本和关键的过程的基础，即，动物的蛋如何知道将头部和脊柱结构放置在哪里，以及它是如何进行的。核糖核酸（RNA）是所有细胞的基本组成部分。我们正在研究一种RNA，它的位置可以预测斑马鱼发育过程中头部和背部结构的形成位置。错置RNA或阻断RNA的功能会导致鱼类胚胎缺乏这些重要部分。因此，这种RNA在这种生物的头部和脊柱结构的形成中起着非常关键的作用。我们现在想要精确地了解RNA是如何控制这些事件的。类似的rna也存在于人类体内。我们用斑马鱼作为模型生物来理解这一过程，因为我们可以获得胚胎在母体体外受精和发育，这使我们能够观察这些过程的发生，无论是在正常条件下还是在各种方式的干扰下。我们将对RNA进行各种改变，并观察这些改变如何影响头部和脊柱结构的形成。具体来说，我们要么移除RNA中的某些片段，要么通过打乱片段来改变它们，以了解这些片段是否对RNA在形成头部和脊髓的功能至关重要。由于早期的鱼胚胎在光学上是清晰的，我们可以通过拍摄视频以非侵入性的方式观察RNA在活体样本中移动到正确位置的过程。斑马鱼一次可以产下数百个卵，这一特点使我们可以很容易地提取RNA和任何与之结合的东西。通过了解哪些因素与RNA相关，我们可以深入了解它的功能。由于人类中也存在类似的rna，因此这些rna的功能障碍可能会导致出生缺陷。因此，提议的项目解决了一个非常基本的问题，并对人类先天性出生缺陷有影响。

The proposed project aims to understand the basis of a very fundamental and crucial process, i.e., how does the egg of an animal know where to place the head and spine structures, and how does it go about it. Ribonucleic acids (RNA) are an essential component of all cells. We are working on an RNA whose location predicts where the head and back structures will form in developing zebrafish. Misplacing the RNA or blocking the functions of the RNA results in fish embryos lacking these essential parts. Therefore, this RNA has a very crucial role in formation of the head and spine structures in this organism. We now want to understand precisely how the RNA controls these events. Similar RNAs exist in humans as well. We use the zebrafish as a model organism to understand this process because we can obtain embryos are externally fertilized and develop outside the body of the mother, which allows us to watch these processes as they take place, both under normal conditions and upon perturbation by various means. We will make various changes in the RNA and observe how these changes affect formation of head and spine structures. Specifically, we will either remove certain segments in the RNA or alter them by scrambling the segments, to learn if these segments are crucial to the function of the RNA in making the head and spinal cord. Since early fish embryos are optically clear, we can observe the RNA as it moves to its correct location in live samples in a non-invasive manner by taking videos. Zebrafish can lay hundreds of eggs at a time, a feature that allows us to easily extract the RNA and anything that binds to it. By knowing which factors are associated with the RNA, we can get insights into how it may function. Since similar RNAs exist in humans, it is possible that dysfunctions of such RNAs might result in birth defects. Therefore, the proposed project addresses a very fundamental question, and has implications for human congenital birth defects.