Evolutionary Gain of Dbx1 Expression Drives Subplate Identity in the Cerebral Cortex

Abstract

Summary: Changes in transcriptional regulation through cis-regulatory elements are thought to drive brain evolution. However, how this impacts the identity of primate cortical neurons is still unresolved. Here, we show that primate-specific cis-regulatory sequences upstream of the Dbx1 gene promote human-like expression in the mouse embryonic cerebral cortex, and this imparts cell identity. Indeed, while Dbx1 is expressed in highly restricted cortical progenitors in the mouse ventral pallium, it is maintained in neurons in primates. Phenocopy of the primate-like Dbx1 expression in mouse cortical progenitors induces ectopic Cajal-Retzius and subplate (SP) neurons, which are transient populations playing crucial roles in cortical development. A conditional expression solely in neurons uncouples mitotic and postmitotic activities of Dbx1 and exclusively promotes a SP-like fate. Our results highlight how transcriptional changes of a single fate determinant in postmitotic cells may contribute to the expansion of neuronal diversity during cortical evolution. : Arai et al. report that primate-specific cis-regulatory elements induce Dbx1 expression in pallial progenitors and neurons. Dbx1 in progenitors and/or neurons promotes specific identities of key players in cerebral cortex development, Cajal-Retzius and subplate neurons. Transcriptional changes of a single fate determinant contribute to transient neuron diversity in cortical evolution. Keywords: Dbx1, postmitotic, primate-specific cis-regulatory elements, Cajal-Retzius neurons, subplate neurons, cortical evolution