Somatic gene repression ensures physical segregation of germline and soma in Drosophila embryos.

In many animals, primordial germ cells are transiently segregated outside the somatic-cell cluster that forms the embryo's body during early embryogenesis. This physical segregation of the germline from the soma has long been believed to be crucial for germline development, but the mechanisms controlling this segregation and its developmental significance remain unclear. Here, in Drosophila, we show that somatic gene silencing in the germline is essential for maintaining this segregation. Primordial germ cells (pole cells) lacking the Nanos- and Polar granule component (Pgc)-dependent dual repression mechanism misexpress widespread somatic genes. They form abnormal cellular protrusions, invade adjacent somatic epithelium, and intermingle with somatic cells. These mislocalized pole cells ultimately undergo cell death, whereas properly segregated cells survive. Notably, knockdown of miranda (mira), one of the somatic genes ectopically expressed, rescues these phenotypes. Our findings uncover a previously unrecognized mechanism whereby somatic gene silencing safeguards the physical boundary between the germline and the somatic cells forming the embryo's body, highlighting its potential role in ensuring germline viability during early development.