TGIF1, a new player in female gonadal development

Estermann MA, Major AT, Hirst CE and Smith CA

Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.

The embryonic gonad is the only organ inside our body with the ability to transform into two completely different organs: Testis or Ovaries. We use the chicken as a model organism to understand these processes. In developing chicken embryos, the gonads form on the medioventral surface of the mesonephric kidneys at embryonic day (E) 3, equivalent to Hamburger and Hamilton stage (HH) 19. At this stage, they are undifferentiated or bipotential. At E6 (HH29), gonads begin morphological differentiation into testes in ZZ embryos or unilateral ovary in ZW embryos. A previous gonadal sex differentiation RNA-seq experiment performed in our lab revealed that Transforming growth-induced factor 1 (TGIF1) is differentially expressed between males and females after the onset of sex differentiation, with higher levels in female gonads at embryonic day 6 (stage 29 HH). TGIF1 belongs to the superfamily of TALE homeodomain proteins that control many biological processes, including embryonic development, cell proliferation, and differentiation. To characterize the expression pattern of TGIF1 in the chicken gonads we performed whole mount in situ hybridization and evaluated transcripts localization in male and female urogenital systems at E4.5, E6.5 and E8.5. We found stronger gonadal staining in females than males after sex differentiation (E6.5 and E8.5). To evaluate the possible role in female gonadal differentiation processes we performed overexpression experiments. Preliminary results show that overexpression in male gonads turned them into a more female phenotype. This is the first report of TGIF1 playing a role in gonadal differentiation. We hypothesize that TGIF1 is one of the master genes controlling female gonad development.