Maternal Nanos inhibits Importin-α2/Pendulin-dependent nuclear import to prevent somatic gene expression in the Drosophila germline

Abstract

Repression of somatic gene expression in germline progenitors is one of the critical mechanisms involved in establishing the germ/soma dichotomy. In Drosophila, the maternal Nanos (Nos) and Polar granule component (Pgc) proteins are required for repression of somatic gene expression in the primordial germ cells, or pole cells. Pgc suppresses RNA polymerase II-dependent global transcription in pole cells, but it remains unclear how Nos represses somatic gene expression. Here, we show that Nos represses somatic gene expression by inhibiting translation of maternal importin-α2 ( impα2) mRNA. Mis-expression of Impα2 caused aberrant nuclear import of a transcriptional activator, Ftz-F1, which in turn activated a somatic gene, fushi tarazu ( ftz), in pole cells when Pgc-dependent transcriptional repression was impaired. Because ftz expression was not fully activated in pole cells in the absence of either Nos or Pgc, we propose that Nos-dependent repression of nuclear import of transcriptional activator(s) and Pgc-dependent suppression of global transcription act as a ‘double-lock’ mechanism to inhibit somatic gene expression in germline progenitors.

Author summary

Identification of the molecular mechanism underlying germline segregation from the soma is a fundamental goal of reproductive, cellular, and developmental biology. In many animal species, repression of somatic gene expression in germline progenitors is critical for the germ/soma segregation. In Drosophila, germ plasm, a specialized ooplasm partitioned into germline progenitors, contains maternal factors sufficient to repress somatic differentiation. Here, we show that a subset of somatic genes is derepressed when two maternal factors, Nanos (Nos) and Polar granule component (Pgc) are concomitantly suppressed. While Pgc is known to suppress RNA polymerase II (Pol II) activity, how Nos achieves this effect remains obscure. We find that Nos represses production of Importin-α2 that is essential for nuclear import of transcriptional activators for somatic gene expression in germline progenitors. Thus, we propose that Nos-dependent inhibition of nuclear import of transcriptional activators and Pgc-dependent suppression of Pol II activity acts as a ‘double-lock’ mechanism to ensure tight inhibition of somatic gene expression in germline progenitors. Since Nos is evolutionarily conserved, and a transient suppression of Pol II is a trait of germline progenitors of diverse animal species, the ‘double-lock’ mechanism may play a widespread role in germ/soma segregation.