A pilgrim's progress: Seeking meaning in primordial germ cell migration

- Mechanisms of PGC migration vary by organism, though the process is highly conserved.
- Migratory PGCs may gain a proliferative edge by being first to reach pro-mitotic soma.
- Cell competition during migration may select PGCs based on relative fitness.
- Extragonadal germ cell tumors may arise from heterogeneous PGC migration and survival.

Comparative studies of primordial germ cell (PGC) development across organisms in many phyla reveal surprising diversity in the route of migration, timing and underlying molecular mechanisms, suggesting that the process of migration itself is conserved. However, beyond the perfunctory transport of cellular precursors to their later arising home of the gonads, does PGC migration serve a function? Here we propose that the process of migration plays an additional role in quality control, by eliminating PGCs incapable of completing migration as well as through mechanisms that favor PGCs capable of responding appropriately to migration cues. Focusing on PGCs in mice, we explore evidence for a selective capacity of migration, considering the tandem regulation of proliferation and migration, cell-intrinsic and extrinsic control, the potential for tumors derived from failed PGC migrants, the potential mechanisms by which migratory PGCs vary in their cellular behaviors, and corresponding effects on development. We discuss the implications of a selective role of PGC migration for in vitro gametogenesis.

258