REGULATION OF THE WILMS-TUMOR GENE DURING SPERMATOGENESIS

Spermatogenesis is the process by which male germ cells develop and ma ture, a pathway that includes a transition from a mitotic to a meiotic cell cycle, Throughout this pathway, the germ cells are in close cont act with their nurturing cells, the Sertoli cells, Sertoli-germ cell i nteractions are difficult to study in mammals due to the complex cellu lar organization of their seminiferous tubules. The urodele amphibian testis, however, provides a unique system to study the process of germ cell maturation; it is organized in a gradient-like cystic structure, in which synchronized germ cells can be found within the same cyst, T he Wilms' tumor gene (WT1) has been shown to be an essential gene for the formation of the gonads in mice, and it has been implicated in a v ariety of differentiation processes, The WT1 gene is thus a good candi date for the study of the differentiation processes involved in the ma turation of the male germ cells, By using a probe for the urodele WT1 homologue in in situ hybridization studies, as well as an antibody aga inst the WT1 protein in immunohistochemistry studies, we determined th at WT1 gene expression in Sertoli cells depends on the stage of matura tion of the associated germ cell, Thus, WT1 mRNA was detected only in Sertoli cells of cysts that contained early spermatogonia. No mRNA exp ression was observed in cysts containing late spermatogonia, germ cell s undergoing meiosis, or germ cells going through spermiogenesis. Immu nohistochemistry studies confirmed that WT1 protein was strongly expre ssed in Sertoli cells associated with early spermatogonia but not in l ate ones, The protein was also found in Sertoli cells associated with germ cells that undergo the subsequent stages of meiosis and spermioge nesis, These results suggest that WT1 could be involved in the regulat ion by Sertoli cells of germ cell maturation and possibly in the progr ession from a mitotic to a meiotic cell cycle. (C) 1996 Wiley-Liss, In c.