Bioactive isoprenoids guide migrating germ cells to the embryonic gonad

Germ cells are essential to sexual reproduction. Across the animal kingdom, extracellular signaling isoprenoids, such as retinoic acids (RAs) in vertebrates and juvenile hormones (JHs) in invertebrates, facilitate multiple processes in the germline lifecycle. Here we investigated the role of these potent signaling molecules in embryonic germ cell migration, using JHs in Drosophila melanogaster as a model system. In contrast to their established endocrine roles during larval and adult germline development, we found that JH signaling acts locally during embryonic development. Using an in vivo biosensor, we found JH signaling is first active near primordial germ cells (PGCs) as they migrate to the developing somatic gonad. Through in vivo and in vitro assays, we found that JHs are both necessary and sufficient for PGC migration. Analysis into the mechanisms of this newly uncovered paracrine JH function revealed that PGC migration was compromised when JHs were reduced or increased, suggesting that specific titers or spatiotemporal JH dynamics are required for robust PGC colonization to the gonad. Compromised PGC migration can impair fertility and cause germ cell tumors in many species, including humans. In mammals, retinoids, a JH-related family of signaling isoprenoids, has many roles in development and reproduction. We found that retinoic acid, like JH, was sufficient to impact PGC migration in vitro. Together, our study reveals a previously unanticipated role of isoprenoids as local effectors of pre-gonadal PGC development and suggests a broadly shared mechanism in PGC migration. HighlightsO_LIJuvenile hormones (JH) are necessary & sufficient for Primordial Germ Cell (PGC) migration. C_LIO_LIJH signaling acts directly in and around migrating PGCs prior to its endocrine function. C_LIO_LICompensatory feedback sensitive to JH receptor function maintains JH homeostasis. C_LIO_LIJH-like retinoic acids may have similar roles during mammalian germ cell migration. C_LI