Arp. Beck et al., RNA-BINDING PROTEIN TIAR IS ESSENTIAL FOR PRIMORDIAL GERM-CELL DEVELOPMENT, Proceedings of the National Academy of Sciences of the United Statesof America, 95(5), 1998, pp. 2331-2336
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.