Nature, Published online: 18 March 2026; doi:10.1038/s41586-026-10226-y

The excitatory neuron diversity and specialized connectivity of complex, multilayered mammalian neocortex are driven by mammalian-specific cis-regulatory elements bound by ZBTB18, deletion of which disrupts gene expression and results in projection patterns resembling those of non-mammalian brains.