Blimp1 and the emergence of the germ line during development in the mouse.

To elucidate the mechanism for the specification of primordial germ cells (PGCs) in mice, we have developed and exploited the methods of single cell analysis. Based on these studies, we proposed a molecular program associated with this process, a key event of which is the repression of homeobox genes that are, without exception, upregulated in somatic neighbors. We have now identified Blimp1, a potent transcriptional repressor of a histone methyltransferase subfamily, as a key regulator of PGC specification. Indeed, the unexpected early onset of Blimp1 expression in a few cells at the most proximal-posterior epiblast cells marks the origin of the germ cell lineage. Disruption of Blimp1 function resulted in aberrant PGC-like cells with a deregulated intrinsic gene expression program at a very early stage, which demonstrates that Blimp1 is a critical determinant of the germ line in mice.