Dmrt2 regulates sex-biased neuronal development in the cingulate cortex

Sexual differences are prevalent in the brain. DMRT transcription factors have been postulated as important determinants of sex differences. Previous research focused on the DMA subfamily in the brain. Here, we reveal an unprecedented role for Dmrt2 in regulating the proliferation and development of cortical neurons in mice. Dmrt2 is expressed in deep-layer neurons of the cingulate cortex (CgCx) throughout development. Its downregulation in the CgCx primordium results in premature cell cycle exit of embryonic progenitors and subsequent reduction in cortical plate cellular density at later developmental stages. Dmrt2 expression is higher in male embryos during early development, potentially explaining their increased vulnerability to Dmrt2 depletion. As development progresses, Dmrt2 expression persists in deep-layer neurons, controlling processes like migration, axonal targeting, and neuronal-specific gene expression. This study broadens our understanding of Dmrt2 gene function in the brain and provides insights into the molecular basis of sexual differences in neurodevelopmental processes.