DMRT2 participates in chicken gonadal development by regulating CHUK and SOX9-mediated cell proliferation and apoptosis.

Understanding sex determination mechanism is crucial for elucidating sexual evolution and sex control in animal husbandry. In this study, data showed that doublesex and mab-3 related transcription factor 2 (DMRT2) expression in gonads was developmentally regulated in a sex- and lateralization-specific manner. The nuclear localization signal of DMRT2 was identified, showing high expression in the female gonadal cortex. Transcriptome and chromatin immunoprecipitation followed by sequencing (ChIP-seq) analyses screened and validated target genes (component of inhibitor of nuclear factor kappa B kinase complex (CHUK) and SRY-box transcription factor 9 (SOX9)) and downstream signaling pathways (e.g., sex determination, cell apoptosis, and inflammation related). It was also validated that DMRT2 could promote cell proliferation and inhibit apoptosis. The effect of DMRT2 on apoptosis and inflammation was mediated by CHUK. These factors may potentially regulate apoptosis pathway and Wnt signaling pathway. In conclusion, DMRT2 participates in sex differentiation and development of chicken gonads by regulating proliferation, apoptosis, and inflammatory pathways through target genes such as CHUK and SOX9. The novel mechanism of DMRT2 regulating avian gonadal differentiation and development may deepen understanding of vertebrate sexual evolution and facilitate sex control in poultry.