A NOVEL MEMBER OF THE TRANSMEMBRANE SERINE THREONINE KINASE RECEPTOR FAMILY IS SPECIFICALLY EXPRESSED IN THE GONADS AND IN MESENCHYMAL CELLS ADJACENT TO THE MULLERIAN DUCT/

The activin and TGF-beta type II receptors are members of a separate s ubfamily of transmembrane receptors with intrinsic protein kinase acti vity, which also includes the recently cloned TGF-beta type I receptor . We have isolated and characterized a cDNA clone (C14) encoding a new member of this subfamily. The domain structure of the C14-encoded pro tein corresponds with the structure of the other known transmembrane s erine/threonine kinase receptors. It also contains the two inserts in the kinase domain that are characteristic for this subfamily. Using in situ hybridization, C14 mRNA was detected in the mesenchymal cells lo cated adjacent to the mullerian ducts of males and females at day 15 ( E15) of embryonic development. Marked C14 mRNA expression was also det ected in the female gonads. In female E16 embryos, the C14 mRNA expres sion pattern remained similar to that in E15 embryos. However, in male E16 embryos C14 mRNA was detected in a circular area that includes th e degenerating mullerian duct. The expression of C14 mRNA was also stu died using RNase protection assays. At E15 and E16, C14 mRNA is expres sed in the female as well as in the male urogenital ridge. However, at E19, a high C14 mRNA level in the female urogenital ridge contrasts w ith a lack of C14 mRNA in the male urogenital ridge. This correlates w ith the almost complete degeneration of the mullerian ducts in male em bryos at E19. C14 mRNA expression was also detected in embryonic teste s at E15, E16 and E19 using RNase protection assays, but at much lower levels than those found in the developing ovaries. In eleven other ti ssues no C14 mRNA was observed. The results point to anti-mullerian ho rmone (AMH) being the most likely candidate ligand for C14. The embryo nic C14 mRNA expression pattern in the urogenital ridge correlates wit h the expected site of AMH action, and C14 mRNA expression in the feta l ovary is in agreement with known effects of AMH on gonadal different iation. Postnatal C14 mRNA expression in rats was found to be confined mainly to the gonads. In the testis, C14 mRNA expression occurs in Se rtoli cells. This testicular expression markedly increases during the first 3 weeks after birth, concurrent with the onset of spermatogenesi s.