RNA-BINDING PROTEIN TIAR IS ESSENTIAL FOR PRIMORDIAL GERM-CELL DEVELOPMENT

Primordial germ cells (PGCs) give rise to both eggs and sperm via comp lex maturational processes that require both cell migration and prolif eration, However, little is known about the genes controlling gamete f ormation during the early stages of PGC development, Although several mutations are known to severely reduce the number of PGCs reaching and populating the genital ridges, the molecular identity of only two of these genes is known: the c-kit receptor protein tyrosine kinase and t he c-kit ligand (the steel factor), Herein, we report that mutant mice lacking TIAR, an RNA recognition motif/ribonucleoprotein-type RNA-bin ding protein highly expressed in PGCs, fail to develop spermatogonia o r oogonia, This developmental defect is a consequence of reduced survi val of PGCs that migrate to the genital ridge around embryonic day 11. 5 (E11.5), The numbers of PGCs populating the genital ridge in TIAR-de ficient embryos are severely reduced compared to wild-type embryos by E11.5 and in the mutants PGCs are completely absent at E13.5. Furtherm ore, TIAR-deficient embryonic stem cells do not proliferate in the abs ence of exogenous leukemia inhibitory factor in an in vitro methylcell ulose culture assay, supporting a role for TIAR in regulating cell pro liferation. Because the development of PGCs relies on the action of se veral growth factors, these results are consistent with a role for TIA R in the expression of a survival factor or survival factor receptor t hat is essential for PGC development, TIAR-deficient mice thus provide a model system to study molecular mechanisms of PGC development and p ossibly the basis for some forms of idiopathic infertility.