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 germline from the soma has been long 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. We showed that primordial germ cells (pole cells) lacking the Nanos- and Polar granule component (Pgc)-dependent dual repression mechanism caused misexpression of widespread somatic genes. They formed abnormal cellular protrusions, invaded adjacent somatic epithelium, and intermingled with somatic cells. These mislocalized pole cells ultimately underwent cell death, whereas properly segregated cells survived. Notably, the knockdown of miranda ( mira ), one of the somatic genes expressed ectopically in the pole cells lacking this repression mechanism, rescued these phenotypes. Our findings provide the first evidence that somatic gene silencing in germline is essential for preserving the physical segregation between germline and soma, highlighting its role in ensuring germline viability during early development.