Journal
STEM CELL RESEARCH
Volume 11, Issue 2, Pages 845-860Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.scr.2013.05.012
Keywords
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Funding
- Ministry of Science and Technology of China [2010CB945403]
- National Natural Science Foundation of China [30971522]
- Science and Technology Commission of Shanghai Municipality [11DZ2260300]
- Innovation Program of Shanghai Municipal Education Commission [10ZZ34]
- Shanghai Pujiang Program [10PJ1403000]
- Eunice Kennedy Shriver NICHD/NIH [U01-HD060496]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [U01HD060496] Funding Source: NIH RePORTER
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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 early germ cell 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 adult 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 both human and murine ESCs. In contrast, Gasz deficiency resulted in pronounced reduction of germ cells during ESC differentiation and decreased expression of MVH and DAZL in genital ridges during early embryonic development. Further analyses demonstrated that GASZ interacted with DAZL, a key germ cell regulator, to synergistically promote germ cell derivation from ESCs. Thus, our data reveal a potential role of GASZ during embryonic germ cell development and provide a powerful in vitro system for dissecting the molecular pathways in early germ cell formation during embryogenesis. (C) 2013 Elsevier B.V. All rights reserved.
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