Maternal Rbm24a orchestrates temporal organization and maintains homeostasis of germ granules to safeguard germ cell fate

<title>Abstract</title> <p>The fate of primordial germ cells (PGCs) in many animals critically depends on maternal germ granules, yet how their organization and function are temporally orchestrated remains largely elusive. Here, by establishing a leakage-free auxin-inducible degron (AID) system in zebrafish, we stage-specifically depleted maternal Rbm24a, a key germ granule component, and revealed its sequential functions in post-assembled germ granules. In PGC precursors, Rbm24a–mediated anchorage of germ plasm mRNAs prevents their degradation. During PGC migration, these germ plasm mRNAs progressively exit perinuclear germ granules for translation into proteins to maintain germ granule integrity and PGC fate. Loss of Rbm24a causes sequential premature mRNA release and degradation, collapse of germ granule, PGC transdifferentiation, and infertility. Building on these insights, we further established a two-line breeding strategy targeting Rbm24a at zygotic genome activation (ZGA) to generate sterile hybrids. These findings uncover an important temporal mechanism governing germ granule homeostasis to safeguard PGC fate.</p>