Segregation of the mouse germline and soma.

Mouse primordial germ cells (PGCs), originate from the early post-implantation epiblast in response to BMP4 secreted by the extraembryonic ectoderm. However, how BMP4 acts here has remained unclear. Recent work has identified the transcription factor (TF), OTX2 as a key determinant of the segregation of the germline from the soma. OTX2 is expressed ubiquitously in the early post-implantation epiblast, decreasing rapidly in cells that initiate the PGC programme. Otx2 mRNA is also rapidly repressed by BMP4 in vitro, in germline competent cells. Supporting a model in which BMP4 represses Otx2, enforcing sustained OTX2 expression in competent cells blocks germline entry. In contrast, Otx2-null epiblast cells enter the germline with increased efficiency in vitro and in vivo and can do so independently of BMP4. Also, Otx2-null cells can initiate germline entry even without the crucial PGC TF, BLIMP1. In this review, we survey recent advances and propose hypotheses concerning germline entry.