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Abstract

Neuronal function is highly dependent upon dendritic and axonal processes that enable an extensive network of connections between neurons and is essential in the process of synaptic integration and signal transmission. The precise morphology of neurons allows the nervous system to operate functionally because of their established connectivity. Recent studies have identified many genes that regulate dendrite morphogenesis in genetic model systems such as Drosophila melanogaster (the fruit fly) and Caenorhabditis elegans (the worm). For example, rbm-39, which encodes an RNA-binding motif protein, has recently been revealed to play a role in dendrite development in worms, while the fruit fly homolog of this gene, caper, has been shown to be important for various aspects of nervous system development and function. The extent of the role of rbm-39 in nervous system development, however, is still unknown. Using a strain of C. elegans that had the rbm-39 gene removed by CRISPR genome-editing technology, we examined the role of rbm-39 in various neuron and glia subtypes. Specific neurons/glia were quantitatively analyzed and compared between the rbm-39 mutant and the control worm. Our results suggest that rbm-39 has surprisingly minimal impacts on nervous system development compared to the role of its homolog in the fruit fly. Previous studies suggest that RBM-39 family proteins are involved in alternative splicing and other mechanisms of gene regulation. To learn more about the molecular role of the RBM-39 protein, we isolated and sequenced mRNA from rbm-39 mutants and controls to identify differentially expressed and differentially spliced targets. The results from the sequencing strongly suggest that RBM-39 plays a role in the regulation of gene expression, and more specifically in the regulation of alternative splicing. Consistent with a role in nervous system development, our results show the rbm-39 regulates many genes with known specific functions in the nervous system and its morphology. Additionally, RBM-39 homologs are found in humans, so a deeper understanding of this protein in worms and flies could help further illuminate RBM-39 function in the context of human neuronal development.

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