RT Journal Article
SR Electronic
T1 Correction of β3 integrin haplo-insufficiency by CRISPRa normalizes cortical network activity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 664706
DO 10.1101/664706
A1 Fanny Jaudon
A1 Agnes Thalhammer
A1 Lorenzo A. Cingolani
YR 2019
UL http://biorxiv.org/content/early/2019/06/10/664706.abstract
AB The extracellular matrix (ECM) plays an essential role in regulating the function of neuronal networks. In many cell types, the ECM exerts its effects through the transmembrane receptors integrins. Here, we investigate whether neuronal integrins regulate network excitability. Specifically, we focus on β3 integrin, which has been associated to autism spectrum disorder and whose expression in neurons is regulated by activity. We have designed CRISPRa tools to titrate β3 integrin expression in neurons. By using multi-electrode arrays and Ca2+imaging, we show that β3 integrin boosts network excitability and synchrony in primary cortical neurons. Crucially, CRISPRa could compensate precisely for β3 integrin haplo-insufficiency, thereby rebalancing level and correlation of neuronal activity. By contrast, rescue strategies based on exogenous gene expression resulted in hyper-active networks firing in unison. Thus, regulation of β3 integrin by CRISPRa provides a precise and efficient system for modulating neuronal network function.