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Background   Dmrt1  is a highly conserved gene involved in the determination and early differentiation phase of the primordial gonad in vertebrates. In the fish medaka  dmrt1bY , a functional duplicate of the autosomal  dmrt1a  gene on the Y-chromosome, has been shown to be the master regulator of male gonadal development, comparable to  Sry  in mammals. In males mRNA and protein expression was observed before morphological sex differentiation in the somatic cells surrounding primordial germ cells (PGCs) of the gonadal anlage and later on exclusively in Sertoli cells. This suggested a role for  dmrt1bY  during male gonad and germ cell development.    Results  We provide functional evidence that expression of  dmrt1bY  leads to negative regulation of PGC proliferation. Flow cytometric measurements revealed a G2 arrest of  dmrt1bY  expressing cells. Interestingly, also non-transfected cells displayed a significantly lower fraction of proliferating cells, pointing to a possible non-cell autonomous action of dmrt1bY. Injection of antisense morpholinos led to an increase of PGCs in genetically male embryos due to loss of proliferation inhibition.    Conclusion  In medaka,  dmrt1bY  mediates a mitotic arrest of PGCs in males prior to testes differentiation at the sex determination stage. This occurs possibly  via  a cross-talk of Sertoli cells and PGCs.

Inhibition of primordial germ cell proliferation by the medaka male determining gene Dmrt1bY