Affiliations: 1) New York University, Skirball Institute; 2) Baruch College, CUNY; 3) The Whitehead Institute, MIT
Keywords: e. primordial germ cells; n. hormonal control
Proper germ cell development is crucial for the health and fertility of subsequent generations. Emerging evidence suggests that secreted isoprenoids, such as retinoic acids (RAs) in vertebrates and juvenile hormones (JHs) in insects, impact several aspects of fertility. However, the mechanisms by which these potent molecules support reproductive development remain unclear. Here, we sought to elucidate the functions of JHs in primordial germ cell development. We made a GFP-based JH reporter, which revealed that JH signaling is first active in the Drosophila embryonic mesoderm as primordial germ cells emerge from the endoderm and begin to migrate within the mesoderm toward the somatic gonad. Consistent with this germ cell-proximal signaling pattern and previous work (Niwa, et al., 2008), we find that expression of a gene encoding the key JH biosynthesis enzyme, jhamt, is enriched near germ cells as they migrate toward the gonad and that JH degradation enzymes are expressed in areas that germ cells migrate away from. By generating several new double and triple mutant animals, we find that both JH biosynthesis and degradation enzymes are required for germ cells to efficiently colonize the developing somatic gonad. Together, these data suggest that JHs, which act systemically in larval and adult animals, act locally in the Drosophila embryo and that local dynamics in JH bioavailability may be needed to facilitate germ cell migration. To isolate autonomous vs non-autonomous requirements, we turned to an in vitro migration assay using primordial germ cells isolated by FACS, finding that pure JH III or the JH mimic, methoprene, is sufficient for germ cell migration in vitro. Interestingly, results from several experiments suggest that this newly uncovered function for JHs does not involve classical, nuclear receptor-mediated transcription, but rather calcium-linked cytosolic factor, phospholipase C. Collectively, these findings add to the growing appreciation of the diverse roles of secreted steroid and isoprenoids throughout the germline lifecycle in species that span both invertebrates and vertebrates. In mice, enzymes that synthesize RAs are also expressed in the developing somatic gonad as germ cell colonize this tissue. We find that, like JH in Drosophila, RA is sufficient for mouse germ cell migration in vitro, leaving open the possibility that this newly uncovered role in reproductive development may be conserved.