Chromatin remodeler <i>Arid1a</i> regulates subplate neuron identity and wiring of cortical connectivity
Daniel Z. Doyle, Mandy M. Lam, Adel Qalieh, Yaman Qalieh, Alice Sorel, Owen H. Funk, Kenneth Y. Kwan
Abstract
Significance The cognitive, perceptive, and motor capabilities of the mammalian cerebral cortex depend on assembly of circuit connectivity during development. Subplate neurons, strategically located at the junction of gray and white matter, orchestrate the wiring of cortical circuits. Using a genetic approach to study gene necessity and sufficiency in subplate neurons, we uncover an essential role for chromatin remodeler Arid1a in subplate neuron gene expression and axon guidance functions. Cortical deletion of Arid1a disrupts subplate-dependent formation of corpus callosum, targeting of thalamocortical axons, and development of sensory maps. Together, our study identifies Arid1a as a central regulator of subplate-dependent axon pathfinding, establishes subplate function as essential to callosum development, and highlights noncell-autonomous mechanisms in neural circuit formation and disorders thereof.