A Nanos3-containing protein complex can activate RNA translation in primordial germ cells in vivo.

Maintaining the germline fate requires tight post-transcriptional control of RNA function. Here, we investigate how primordial germ cell (PGC) identity is maintained in zebrafish and reveal that the conserved RNA-binding proteins Nanos3 and Dead End1 form a complex that safeguards PGC identity. Using transcriptomics and in vivo imaging-based analyses, we show that this complex controls the translational activation and localization of both nanos3 and dead end1 RNAs, establishing a positive feedback loop crucial for regulating their protein expression. These findings uncover a previously unknown layer of control over germline development, where a complex containing Nanos3, a protein associated with the inhibition of RNA translation, acts as an activator by interacting with an eIF3 complex protein to promote translation, thereby maintaining specific RNAs at the periphery of phase-separated germ cell granules. Disrupting the physical interaction between Nanos3 and Dead End1 leads to transdifferentiation of germ cells into somatic lineages. Overall, our findings identify a self-sustaining mechanism of translational activation in vivo, positioning the Nanos3-Dead End1 complex as a central effector of germline fate.