Endothelial SHANK3 regulates tight junctions in the neonatal mouse blood-brain barrier through β-Catenin signaling

Authors: Yong-Eun Kim, Minseong Kim, Sunwhi Kim, Raham Lee, Yusuke Ujihara, Esther Magdalena Marquez-Wilkins, Yong-Hui Jiang, Esther Yang, Hyun Kim, Changhoon Lee, Changwon Park, and Il Hwan Kim

Nature Communications, 06 February 2025

Scientists investigate the BBB’s role in neurodevelopmental disorders and its potential connection to ASD, using the Maestro Z TEER assay to monitor barrier function in real time in vitro.

Despite rigorous research, the underlying mechanisms of autism spectrum disorder (ASD) remain unclear. In this study, scientists examine the role of SHANK3 in brain endothelial cells and its importance in maintaining tight junctions and blood-brain barrier (BBB) function during early development. The researchers found that SHANK3 deficiency disrupts beta-catenin signaling, leading to changes in BBB permeability in neonatal mice, which may contribute to neuronal and behavioral differences linked to ASD. To monitor barrier function in real-time, scientists used the Maestro Z TEER assay, which offered dynamic insights into endothelial cell tight junction integrity. According to the authors, “We expect that our findings and unique approach with an established experimental platform will serve as a foundation for the growth of research in the realm of ASD pathogenesis originating from neonatal BBB disruption.”