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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 remodelerArid1a in subplate neuron gene expression and axon guidance functions. Cortical deletion ofArid1a disrupts subplate-dependent formation of corpus callosum, targeting of thalamocortical axons, and development of sensory maps. Together, our study identifiesArid1a 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.

Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity