Human Down syndrome fibroblasts exhibit changes in cell motility due to increased adhesion

https://kent-islandora.s3.us-east-2.amazonaws.com/ugresearch/2018/2018all/80/thumbnail.jpgHuman Down syndrome fibroblasts exhibit changes in cell motility due to increased adhesion Paige Cassidy1, Shelby Kelemen1, Sami Bailey B.S.1,Taylor Bumbledare1, Leah Kershner B.S.1, Kristy Welshhans Ph.D1,2 1Department of Biological Sciences, 2School of Biomedical Sciences Kent State University, Kent, Ohio Down syndrome is a common developmental disorder which results from the triplication of human chromosome 21. Intellectual disability is ubiquitous in Down syndrome, but our understanding of the cellular mechanisms underlying this phenotype are limited. Focal adhesions link the extracellular matrix to the intracellular cytoskeleton and regulate cellular motility. Focal adhesions are composed of and regulated by multiple proteins, including paxillin and RACK1. Age, sex and race matched human fibroblasts from an individual with Down syndrome and a healthy individual were plated onto coverslips, allowed to grow to 70% confluency, and then fixed. Immunocytochemistry was performed to stain for paxillin or RACK1, and the fluorescence intensity was quantified using FIJI software. We found that expression of paxillin and RACK1 is increased in human Down syndrome fibroblasts, as compared to control fibroblasts. This data suggests that there is increased adhesiveness in Down syndrome cells, which likely contributes to the cellular abnormalities that are characteristic of this disorder. We are currently investigating how this increase in focal adhesions lead to changes in cellular motility in Down syndrome. These results have implications for not only fibroblasts, but also neurons, because many of the same mechanisms underlie motility of these diverse cell types. Thus, one of the mechanisms contributing to the intellectual disability phenotype of Down syndrome may be changes in adhesion during neural development, which leads to inappropriate neuron migration and axon guidance. These experiments will increase our understanding of Down syndrome and help inform the development of treatments for this disorder.