The germline: familiar and newly uncovered properties

Transplantations of both Drosophila pole cells and mouse primordial germ cells suggest that the pregonadal germline of these two organisms is not pluripotent. In mouse PGCs, however, the potential for activating pluripotency is clearly present, as seen in the relative case of deriving EG cells from migratory-stage PGCs. EG cells are derived from altering the in vitro growth conditions of PGCs by the addition of one factor. Conceivably, straying of PGCs in vivo could also lead to novel fates if they migrated into a suitable environment. Aberrant PGC migration underlies models for the origin of several tumor types. How are migratory-stage PGCs prevented from adopting alternative fates in wild-type development? One solution is to link accurate migration into the gonads with germ cell survival. One mechanism of accomplishing this is through the action of pleiotrophic factors such as Steel. Steel is both a proliferation and migration factor; sterility in Steel mutants is due to poor germ cell survival and improper migration. Networking of migratory PGCs is another mechanism to reduce the chances of individual germ cells straying from the migration path. Postmigratory germ cells apparently undergo another restriction on potency--novel imprinting. Assuming that EG methylation profiles accurately reflect modifications made in their founder PGCs, then "erased" pluripotent EG lines suggest that PGCs can be diverted from the germline lineage. Direct assays on PGCs show that the unmethylated phenotype at Igf2r region 2 is characteristic of late germ cells. The maintenance of germline-like methylation with a switch in PGC fate is somewhat analogous to the situation in lag mutants from Volvox, which retain large gonidial-sized cells that can nevertheless initiate somatic differentiation. Just as it is not possible to readjust cell size with a subsequent change in gonidial differentiation, it may be difficult, without gametogenesis, to reimpose methylation modifications once they have been erased. In addition, the methylation status of some sites/loci may be inconsequential to developmental gene activity in germ cells or EG cells. Recent studies indicate that the methylation imprint at Igf2r is not interpreted at functional level until embryogenesis (51). In summary, we have reviewed some distinctive properties of the development of germ cells, from their early segregation, mitotic and meiotic profile, sex determination, to their migration and sequestration into gonads. Some constraints on development of the germline likely serve to maintain its integrity until maturation, when the gametic genomes must be capable of initiating embryonic development. To accomplish this ultimate goal, germ cells in some organisms may retain a bias towards pluripotency throughout development.(ABSTRACT TRUNCATED AT 400 WORDS)