Seminario INCyL – Esther Serrano

The role of Dmrts in the brain has been focused in the DMA subfamily of DMRTs. Here, we show an unprecedented role for another member of the Dmrt gene family, Dmrt2, in the control of proliferation and neuronal specification of cortical neurons. In the mouse brain, Dmrt2 is broadly expressed, influenced by developmental time and sex. In cortical regions, Dmrt2 is present in several neuron types, including layer VIa, deeper corticothalamic projecting neurons (CThPN) of the cingulate cortex (CiCx) where it is maintained until adulthood. Dmrt2 mRNA downregulation in the cingulate cortex primordium leads to embryonic progenitors’ premature exit from cell cycle and the concomitant reduction of CiCx cellular density. In early embryos, Dmrt2 is expressed at higher levels in males which might be responsible for an exquisite control on how neurons occupy distinct cortical layers. Moreover, we show that Dmrt2 differential expression might responsible for the higher susceptibility of males to Dmrt2 reduction. As development progresses, Dmrt2 is maintained in layer VIa-CiCx neurons where the transcription factor is controlling distinct terminal processes including migration, axonal targeting and general pan-neuronal identity of cells.
 In summary, our study described a novel role for Dmrt2 in the regulation of proliferation, connectivity and neuronal identity in any mammalian nervous system so far. It reveals a possible mechanistic link between the function of a member of the conserved family of DMRTs in sexual susceptibility to mental disorders.