Authors: Mohajeri K, Yadav R, D'haene E, Boone PM, Erdin S, Gao D, Moyses-Oliveria M, Bhavsar R, Currall BB, O'Keefe K, Burt ND, Lowther C, Lucente D, Salani M, Larson M, Redin C, Dudchenko O, Aiden EL, Menten B, Tai DJC, Gusella JF, Vergult S, Talkowski ME
The American Journal of Human Genetics, Volume 109, Issue 11, 2022
Scientists investigate the functional effects of MEF2C loss-of-function in vitro using Axion’s noninvasive Maestro Pro MEA platform
Research suggests that MEF2C loss-of-function mutations underlying 5q14.3 microdeletion syndrome are associated with neurodevelopmental conditions including autism spectrum disorder, epilepsy, and hypotonia, but the mechanisms and pathways underpinning this relationship are not well understood. In this study, scientists used CRISPR-engineered human induced pluripotent stem cell (hiPSC)-derived neural stem cells and glutamatergic induced neurons on Axion’s noninvasive, label-free Maestro Pro multielectrode array (MEA) platform, along with other methods, to investigate the topological organization and electrophysiological and transcriptomic consequences associated with structural variants that alter MEF2C expression and regulation. According to the authors, while more research is needed, the overall results show that MEF2C deletion leads to differential expression of genes linked to early neurodevelopmental and synaptic function but “clearly demonstrate that alteration to annotated boundaries of 3D regulatory architecture encompassing established human disease genes is insufficient evidence to presume alterations to gene regulation or phenotypic impact.”
