Functional Analysis Of GASZ In Embryonic Germ Cell Formation

Primordial germ cells (PGCs) are the first germ-line population that forms from the proximal epiblast of the developing embryo. Despite their biological importance, the regulatory networks whereby PGCs arise, migrate, and differentiate into gametes during embryonic development remains elusive, largely due to the limited number of germ cells in the early embryo. To elucidate the molecular mechanisms that govern PGC development, we utilized an in vitro differentiation model of embryonic stem cells (ESCs) and screened a series of candidate genes with specific expression in the reproductive organs. We discovered that gain of function of Gasz, a gene previously reported to participate in meiosis of postnatal spermatocytes, led to the most robust upregulation of PGC formation from either human or murine ESCs. In contrast, Gasz deficiency resulted in pronounced reduction of germ cells during ESC differentiation and MVH+ gonocytes in early embryonic development. Further analyses demonstrated that GASZ interacted with DAZL, a key early germ cell regulator, to synergistically promote PGC derivation from ESCs. Thus, our data reveal a novel role of GASZ during PGC development and will improve our understanding of the molecular regulation of early germ cell formation during embryogenesis.