The regulation and function of miR-124 in ascidian neural development

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Gene regulation typically refers to the process of transcriptional regulation, that is, the controlled production of an RNA molecule, and subsequently a protein, from a gene. Recently a class of small RNAs, called microRNAs, has been shown to regulate gene expression by a different mechanism. In animals, microRNAs control gene activity primarily by repressing the production of proteins from RNAs. Because a single microRNA may regulate hundreds genes, they are thought to play important roles in the development of organisms. In this project, a simple animal, the ascidian, which is closely related to humans, will be used to study the regulation and function of a particular microRNA, called miR-124, which is expressed in the nervous system of animals. Although much is known about microRNA function, previous studies have primarily used cultured cells that have been removed from their normal environment within the tissues of an organism. In contrast, ascidians provide an excellent whole animal environment in which to identify and characterize the genes regulated by this microRNA. This proposal will use an integrated experimental approach employing bioinformatics, molecular genetics and classical embryological methods to investigate miR-124 function. Because these studies will be done using a whole animal approach, it is expected that many novel miR-124 targets will be found (i.e., ones that have been missed in experiments with cultured cells). In addition, this project will examine whether miR-124 mediated gene regulatory mechanisms evolved prior to the appearance of vertebrates (such as mice and humans) and whether ascidians and vertebrates share miR-124 target genes. The detailed analysis provided by this project will lead to a better understanding of microRNA function during nervous system development and will establish the ascidian as an excellent whole animal model for studying microRNA function. This proposal will also provide research opportunities for both undergraduate and graduate students as they train to become the next generation of biological researchers.