PGC-derived migrasomes couple PGC proliferation with migration

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Abstract
The coordination of cell migration and proliferation is essential for embryogenesis and tissue homeostasis. However, the classical gradient signaling model is insufficient to explain how stable mitogenic signaling is maintained within migratory cells. Here, we reveal that primordial germ cells (PGCs) in zebrafish employ migrasomes-vesicular organelles formed during migration-to couple their proliferation with migration, ensuring germline expansion. Migrasomes, generated at retraction fibers via tspan7-dependent biogenesis, deliver the growth factor GDF3 specifically to neighboring PGCs through contact-dependent interactions. GDF3 activates the TGF-β receptor acvr1ba, driving proliferation in a spatiotemporally restricted manner. This homocrine signaling mechanism allows migrating PGCs to autonomously sustain proliferation, circumventing signal dilution in embryonic environments. This work uncovers migrasomes as a bridge linking migration and proliferation, with implications for understanding collective cell behaviors in development and disease.

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