Activin and TGF beta limit murine primordial germ cell proliferation

Mammalian primordial germ cells (PGCs) proliferate as they migrate from the ir initial location in the extraembryonic mesoderm to the genital ridge, th e gonadal anlage. Once in the genital ridge, PGCs cease dividing and differ entiate according to their gender. To identify ligands that might limit PGC proliferation, we analyzed growth factor receptors encoded in RNA obtained from purified germ cells shoaly after their arrival in the genital ridge. Receptors for two members of the TGF beta superfamily were found, TGF beta 1 and activin. As the signal-transducing domains of both receptor systems a re highly conserved, the effects of both TGF beta 1 and activin on PGCs wou ld be expected to be similar. We found that both ligands limited the accumu lation of germ cells in primary PGC cultures. BrdU incorporation assays dem onstrated that either ligand inhibits PGC proliferation. These results sugg est that these signal transduction pathways are important elements of the m echanism that determines germ cell endowment, (C) 1999 Academic Press.