Thalamic NRXN1-Mediated Input to Human Cortical Progenitors Drives Excitatory Neurogenesis

We fuse cortical and thalamic organoids to study this process. Using single-nuclei RNA-sequencing and cellular imaging, we discover that thalamic signals during a progenitor-rich critical period drive developmental gene expression changes and shift cell fate toward increased excitatory neurogenesis.

We find NRXN1 mediates thalamic axon contact with primate-enriched outer radial glia; genetic perturbation of NRXN1 reduces these contacts and significantly attenuates upper-layer neurogenesis. These findings underscore the influence of thalamic input on human cortical radial glia specification, and suggest a novel mechanism for thalamic regulation of human outer radial glia cell fate.