AbstractSubplate neurons indispensably orchestrate the developmental assembly of cortical neural circuits. Here, by cell type-specific dissection of Arid1a function, we uncover an unexpectedly selective role for this ubiquitous chromatin remodeler in subplate neuron molecular identity and circuit wiring function. We find that pan-cortical deletion of Arid1a, but not sparse deletion, leads to mistargeting of callosal and thalamocortical connectivities reminiscent of subplate ablation. These miswiring phenotypes are concomitant with disrupted subplate neuron organization, morphogenesis, axons, and extracellular matrix. Mechanistically, Arid1a is required to establish the transcriptional identity of subplate neurons. Remarkably, cortical plate deletion of Arid1a, which spares subplate neurons, restores subplate axons and extracellular matrix, and is sufficient to extensively correct callosal and thalamocortical axon misrouting, revealing an axon guidance function of Arid1a centered on the subplate. Thus, Arid1a regulates the molecular identity and function of subplate neurons, and thereby non-cell autonomously mediates the formation of cortical connectivity during development.
Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity
