Authors: Jason W. Adams, Annabelle Vinokur, Janaína S. de Souza, Charles Austria, Bruno S. Guerra, Roberto H. Herai, Karl J. Wahlin, and Alysson R. Muotri
Cell Reports, February 27, 2024
Researchers use cortical organoids on Axion’s Maestro MEA platform and other methods to investigate the role of GTF2I in neurodevelopment.
Williams syndrome is a neurodevelopmental disorder caused by the deletion of 26–28 genes in the 7q11.23 chromosomal region and characterized by distinctive hypersocial behaviors, developmental delays, and other issues. Conversely, 7q11.23 duplication syndrome is typically associated with autism, social phobias, and selective mutism. Research suggests that copy-number variations and mutations in one particular gene in the region, GTF2I, may play a role in social behaviors related to Williams syndrome and autism, but the relationship between GTF2I and human neurodevelopment is not well understood.
In this study, scientists used CRISPR-Cas9 to generate GTF2I-KO iPSCs and explore the role of GTF2I in neurodevelopment via neural progenitor cells ([NPCs), human neurons, and cortical organoids. To evaluate the GTF2I-KO organoids in vitro, the team used Axion’s Maestro multielectrode array (MEA) system, finding that the 3D models exhibited decreased activity and synaptic dysfunction in vitro. Overall, the authors show that “alterations in NPCs induced by the loss of GTF2I give rise to neurons and networks with synaptic reduction, reduced electrical activity, and impaired neuronal health” and suggest “that changes in synaptic circuit integrity may be a prominent mediator of the link between alterations in GTF2I and variation in the phenotypic expression of human sociality.” These findings help to shed light on mechanisms underlying variations in human personality and may lead to the development of new therapeutics.
