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

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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.