Signaling pathways controlling primordial germ cell migration in zebrafish.

During their migration, zebrafish primordial germ cells (PGCs) rely on directional cues provided by the chemokine SDF-1a, whose receptor is CXCR4b. The molecular mechanisms whereby CXCR4b activation is interpreted intracellularly into directional migration are not known. Here we investigate the role of two important biochemical pathways -- G-protein-dependent and phosphoinositide 3-kinase (PI3K)-dependent signaling -- in directing PGC migration in zebrafish. We show that G proteins of the Gi family are essential for directional migration but not for PGC motility. Inhibition of PI3K signaling in PGCs slows down their migration and leads to abnormal cell morphology as well as to reduced stability of filopodia. Invariably, during directed PGC migration, the distribution of the products of PI3K activity - phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P(3)] and/or phosphatidylinositol (3,4)bisphosphate [PtdIns(3,4)P(2)] -- is not polarized, and reducing the level of these 3-phosphoinositides does not affect the ability of PGCs to migrate directionally. We therefore conclude that Gi-dependent signaling is essential for directional migration, whereas the PI3K pathway is important for the actual motility of PGCs.