Germ cell specification in mice begins in the epiblast during gastrulation, concomitant with mesoderm induction, but the molecular players required for the subsequent differentiation into germ cells rather than somatic mesoderm have not been well described. In this issue, Hans Schöler and colleagues uncover a role for Hippo signalling in germ cell fate induction. They compare the ability of three previously defined epiblast stem cell (EpiSC) lines to differentiate into germ cells using a standard primordial germ cell-like cell (PGCLC) induction protocol. They find that whereas two of the cell lines are competent to establish PGCLCs, a third related cell line is not. By comparing these lines, the authors identify that the Hippo pathway is upregulated in germ cell-competent EpiSCs, through the nuclear localisation and phosphorylation of the Hippo pathway mediator YAP. Using CRISPR/Cas9 gene editing, they show that Yap is both necessary and sufficient for germ cell fate competence. From these experiments, the authors demonstrate a role for YAP in the activation of WNT signalling, which is known to be crucial for the growth of mesodermal lineages. In summary, this work highlights a key role for Hippo/YAP signalling in germ cell fate induction.
