The dual specificity T-box/bHLH-zipper transcription factor Mga is expressed in pluripotent cells of the mouse embryo and in embryonic stem cells (ESCs), but its function in these cells is unclear. Here, Virginia Papaioannou and colleagues examine the role of Mga in early development and show that it is essential for the survival of pluripotent cells (p. 31). They first show that Mga depletion in early mouse embryos and ESCs causes growth defects; increased cell death is observed in the inner cell mass (ICM) of mutant embryos in vivo and in vitro, and in Mga mutant ESCs cells in vitro. Lineage specification, in contrast, is unaffected by Mga depletion. The researchers further identify the enzyme ornithine decarboxylase (ODC), which converts ornithine to putrescine in the polyamine synthesis pathway, as a candidate downstream target of Mga. Accordingly, they demonstrate that exogenous putrescine can rescue the ICM in Mga mutant embryos and the survival of Mga mutant ESCs. These findings highlight a role for polyamines in pluripotent cells and suggest that Mga controls cell survival in early embryos and ESCs by regulating polyamine pools.