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

像人类、鱼、苍蝇和蠕虫这样的动物是如何进化出在体内产生多种不同细胞和组织类型的能力的？这是发育生物学和自然科学中一个影响深远的问题。我们开始明白，在动物发育过程中，不同组织中特定基因的开启和关闭是决定细胞身份的主要因素。然而，除了简单地打开和关闭基因之外，在将遗传信息从DNA转化为RNA再转化为蛋白质的过程中，还发生了额外的处理层。例如，信使RNA （mRNA）选择性剪接的过程，即从一个前体产生多个成熟mRNA，使细胞多样化的进化途径成为可能。特别是，神经系统的细胞，被称为神经元，相对于其他细胞类型，已经进化出广泛使用选择性剪接，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、发育的生物体中研究神经系统特异性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秀丽隐杆线虫及其最接近的现存亲缘物种来深入了解这一过程。我们在这些可接近的生物中的工作将决定神经系统中的选择性剪接如何进化，它是如何被调节的，以及它如何有助于像我们这样的多细胞动物的细胞多样化。

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.