Yin and Yang relationship of FOXL2 and SOX9 in the maintenance of sexual identity in mammals
During initial phases of sex determination, SRY up-regulates SOX9 expression, and subsequent positive autoregulatory loops involving SOX9 itself. Together with FGF9 and prostaglandin D2 signaling, this activates and maintains Sox9 expression in male gonads, whereas ß-catenin, stabilized by WNT4 and RSPO1 signaling, suppresses SOX9 expression in female gonads.
After birth ß-catenin activity declines and thus in adult female gonads, FOXL2 and estrogen receptors are required to actively repress SOX9 expression to ensure female somatic cell fate.
The transcriptional repression of SOX9 by FOXL2 and estrogen receptors is necessary throughout the lifetime of the female to prevent transdifferentiation of the somatic compartment of the ovary into a testis.