Mediator, a conserved multiprotein complex that connects DNA-bound transcription factors to the RNA polymerase II machinery, is part of the intricate mechanism that regulates eukaryotic transcription. The Med12 mediator subunit is required for gene-specific functions during zebrafish development, but are its developmental functions conserved in mammals? On p. 2723, Heinrich Schrewe and colleagues address this question by examining embryos generated from mouse embryonic stem (ES) cells in which Med12 has been targeted. Embryos generated from Med12 hypomorphic ES cells fail to develop beyond embryonic day 10, the researchers report, and have severe defects in neural tube closure, axis elongation, somitogenesis and heart formation. The Wnt/planar cell polarity pathway and canonical Wnt/β-catenin signalling are both disrupted in the Med12 hypomorphic embryos, they note. Furthermore, embryos generated from Med12 null ES cells fail to establish the anterior visceral endoderm, activate brachyury expression or complete gastrulation. Together, these results indicate that Med12 is necessary for gene-specific functions and for correct Wnt/β-catenin and Wnt/PCP signalling during early mouse development.