The mechanisms, function, and evolution of neuronal alternative splicing in Caenorhabditis species

人、鱼、苍蝇和蠕虫等动物是如何进化出能够创造出在它们体内发现的多种不同细胞和组织类型的呢？这是发育生物学和自然科学中一个影响深远的问题。我们开始认识到，在动物发育过程中，开启和关闭不同组织中的特定基因正在成为细胞特性的主要决定因素。然而，除了简单地打开和关闭基因之外，在将遗传信息从DNA转换到RNA再到蛋白质的过程中，还会发生额外的处理层次。例如，一种被称为信使RNA(MRNA)选择性剪接的过程，即从单一前体产生多个成熟的mRNA，使细胞多样化的替代进化路径成为可能。特别是，神经系统的细胞，称为神经元，已经进化出相对于其他细胞类型的选择性剪接的广泛使用，并且特定的剪接变体已被证明在神经元的发育和生理中发挥作用。然而，尽管它很重要，但在活的、发育中的有机体的背景下，研究神经系统特有的选择性剪接的机制、进化和功能仍然具有挑战性。在目前的提案中，我们将使用微小的线虫及其最接近的近亲物种来更深入地了解这一过程。我们在这些可接触的生物体中的工作将决定神经系统中的替代剪接如何进化，如何受到调控，以及它如何有助于像我们这样的多细胞动物中细胞的多样化。

How have animals such as humans, fish, flies, and worms evolved the capacity to create the many diverse cell and tissue types found in their bodies? This is a far-reaching question in developmental biology and the natural sciences. We are starting to understand that switching specific genes on and off in different tissues is emerging as a major determinant of cell identity during animal development. However, in addition to simply turning on and off genes, additional layers of processing occur in the path of converting genetic information from DNA to RNA to protein. For example, a process known as messenger RNA (mRNA) alternative splicing, where multiple mature mRNAs are produced from a single precursor, has enabled alternative evolutionary paths to cellular diversification. In particular, cells of the nervous system, called neurons, have evolved extensive use of alternative splicing relative to other cell types, and specific splice variants have been shown to play roles in the development and physiology of neurons. However, despite its importance, it remains challenging to study the mechanisms, evolution, and function of alternative splicing specific to the nervous system in the context of a living, developing organism. In the current proposal, we will use the tiny roundworm Caenorhabditis elegans and its closest living relative species to gain a deeper understanding of this process. Our work in these accessible organisms will determine how alternative splicing in the nervous system can evolve, how it is regulated, and how it can contribute to the diversification of cells in multicellular animals like us.