IJMS, Vol. 23, Pages 15496: Sex Lethal Gene Manipulates Gonadal Development of Medaka, Oryzias latipes, through Estrogenic Interventions (International Journal of Molecular Sciences)

Germ cells are pivotal for gonadal sexuality maintenance and reproduction. Sex lethal (sxl), the somatic sex determining gene of Drosophila, is the known regulator and initiator of germ cell femininity in invertebrates. However, the role of the Sxl homologue has rarely been investigated in vertebrates. So, we used medaka to clarify the role of sxl in vertebrate gonadogenesis and sexuality and identified two Sxl homologues, i.e., Sxl1a and Sxl1b. We found that sxl1a specifically expresses in the primordial germ cells (PGC), ovary, (early gonia and oocytes), while sxl1b distributions are ubiquitous. An mRNA overexpression of sxl1a accelerated germ cell numbers in 10 DAH XY fish, and sxl1a knockdown (KD), on the other hand, induced PGC mis-migration, aberrant PGC structuring and ultimately caused significant germ cell reduction in XX fish. Using an in vitro promoter analysis and in vivo steroid treatment, we found a strong link between sxl1a and estrogenic germ cell-population maintenance. Further, using sxl1a-KD and erβ2-knockout fish, we determined that sxl1 acts through erβ2 and controls PGC sexuality. Cumulatively, our study highlights the novel role of sxl1a in germ cell maintenance and sexual identity assignment and thus might become a steppingstone to understanding the commonalities of animal sexual development.