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Puf-A, a nucleolar Puf domain protein, is required for ribosome biogenesis. A study of Puf-A in zebrafish has shown that Puf-A is highly expressed in primordial germ cells (PGCs) and participates in PGC development. However, it remains unclear how Puf-A governs PGC development in mammals. Here, we generated transgenic mice carrying inducible <i>Puf-A</i> shRNA and obtained double heterozygous mice with <i>Puf-A shRNA</i> and <i>Oct4-EGFP</i> to examine the behavior of PGCs. It was found that the knockdown of <i>Puf-A</i> led to the loss of a considerable number of PGCs and a slowdown of the movement of the remaining PGCs. Puf-A and NPM1 colocalized in clusters in the nuclei of the PGCs. The silencing of <i>Puf-A</i> resulted in the translocation of NPM1 from nucleolus to nucleoplasm and the hyperactivation of p53 in the PGCs. The PGCs in <i>Puf-A</i> knockdown embryos showed a significant increase in subpopulations of PGCs at G1 arrest and apoptosis. Moreover, the expression of essential genes associated with PGC maintenance was decreased in the <i>Puf-A</i> knockdown PGCs. Our study showed that Puf-A governed PGC development by regulating the growth, survival, and maintenance of PGCs. We also observed the alterations of NPM1 and p53 upon <i>Puf-A</i> knockdown to be consistent with the previous study in cancer cells, which might explain the molecular mechanism for the role of Puf-A in PGC development.