Evolving Lessons on Metazoan Primordial Germ Cells in Diversity and Development

Germ cells are pivotal for the continuation of biological species. The metazoan germline develops from primordial germ cells (PGCs) that undergo multiple rounds of mitotic divisions. The PGCs are specified by either maternal inheritance of asymmetrically polarized cytoplasmic mRNAs/proteins (found in roundworms, flies, fishes, frogs, and fowl) or via direct induction of epiblast cells from adjacent extraembryonic ectoderm in mammals. In all vertebrates, PGCs remain uncommitted to meiosis and migrate to colonize the developing gonadal ridge before sex determination. Multiple RNA-binding proteins (e.g., Vasa, Dnd, Dazl, etc.) play crucial roles in PGC identity, expansion, survival, and migration. Postsex determination in mouse embryos, Gata4, expressing nascent gonads, induces Dazl expression in newly arriving germ cells that supports retinoic acid-mediated induction of meiotic onset. This article briefly discusses the developmental events regulating the PGC specification and commitment in metazoans. We also highlight the recent progress towards the in vitro generation of functional PGC-like cells in rodents and humans.