Down Syndrome is a complex developmental disorder resulting from the triplication of human chromosome 21. There are many phenotypes of Down Syndrome including distinct facial features, slow wound healing, and intellectual disability. However, our understanding of the mechanisms underlying these phenotypes is limited. Here, we used fibroblasts from individuals that are apparently healthy (euploid fibroblasts) and have Down Syndrome (T21 fibroblasts) to examine changes in cellular morphology and adhesion. We found that there was a significant increase in area and perimeter of the T21 fibroblasts. Because cellular morphology is regulated by adhesion complexes, we next examined focal adhesions, which link the extracellular matrix to the intracellular cytoskeleton. Focal adhesions are made up of many proteins, including paxillin, receptor for activated C kinase 1 (RACK1), vinculin, and talin. We found that all of these proteins were significantly increased in T21 fibroblasts. This implies that there are more focal adhesions in Down Syndrome, which affects cellular morphology and motility. We are currently knocking-down the expression of RACK1 and paxillin to determine if this can rescue the cellular morphology defects in T21 fibroblasts. Notably, these results also have implications for neurons, which use similar mechanisms to regulate cell motility. We have previously demonstrated that overexpression of adhesion proteins in neurons results in decreased axon length, and this could alter neuronal connectivity and contribute to the intellectual disability phenotype of Down Syndrome. Therefore, understanding the mechanisms underlying the altered morphology and adhesion in Down syndrome provides important knowledge about multiple phenotypes of this disorder.
Dr. Kristy Welshhans
Down Syndrome is a complex developmental disorder caused by the triplication of human chromosome 21. It results in many phenotypes including slow wound healing and intellectual disability. To better understand these phenotypes, we used fibroblasts from apparently healthy individuals (euploid fibroblasts) and individuals with Down Syndrome (T21 fibroblasts) to examine changes in cellular morphology and adhesion. We found that there was a significant increase in the area and perimeter of T21 fibroblasts. We also found that members of the focal adhesion complex were significantly increased in T21 fibroblasts. In addition to fibroblasts, these results have implications for neurons, which use similar mechanisms to regulate cell motility. Thus, this research provides important insight into the the molecular and cellular mechanisms underlying multiple phenotypes of Down Syndrome.