Abstract
microRNAs function as genetic rheostats to control gene output. Based on their role as modulators, it has been postulated that microRNAs canalize development and provide genetic robustness. Here, we uncover a novel regulatory layer of chemokine signaling by microRNAs that confers genetic robustness on primordial-germ-cell (PGC) migration. In zebrafish, PGCs are guided to the gonad by the ligand Sdf1a, which is regulated by sequestration receptor Cxcr7b. We find that miR-430 regulates sdf1a- and cxcr7-mRNAs. Using Target Protectors, we demonstrate that miR-430-mediated regulation of endogenous sdf1a and cxcr7b (i) facilitates dynamic expression of sdf1a by clearing its mRNA from previous expression domains, (ii) modulates the levels of the decoy receptor Cxcr7b to avoid excessive depletion of Sdf1a and (iii) buffers against variation in gene dosage of chemokine signaling components to ensure accurate PGC migration. Our results indicate that losing microRNA-mediated regulation can expose otherwise buffered genetic lesions leading to developmental defects.
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