NF1 ALTERNATIVELY SPLICED EXON EXPRESSION CHANGES DURING SCHWANN CELL DIFFERENTIATION FROM MESENCHYMAL STEM CELLS

Abstract

Neurofibromatosis Type 1 (NF1) is a complex, yet relatively common, monogenic disorder that can lead to a variety of detrimental phenotypes. However, the mechanisms behind these manifestations of the disease are still not understood. Neurofibromas are one such hallmark feature; they have been found to consist of a variety of cell types, but the homozygous inactivation of the NF1 gene in Schwann cells specifically has been confirmed to be sufficient for neurofibroma formation. Although Schwann cells and their transformation play a major role in NF1, very few studies have detailed the alternative splicing in the NF1 gene or the effects of NF1 isoform expression in relation to this cell type. The aim of this study was to detect any differences in expression levels of NF1 alternatively spliced exons (ASEs) and Schwann maturation markers as mesenchymal stem cell lines derived from several NF1 swine models differentiate into Schwann cells. The results of this study executed a preliminary assessment of the role played by ASEs over time, but particularly detected some fluctuations of the alternatively excluded exons 4S, 44S, and 51S. Some changes in expression were observed between genotypes and between time points that can be expanded on by further studies.