The mammalian skull vault develops from neural crest and mesodermal-derived mesenchymal cells that migrate over the cerebrum before proliferating and differentiating along an osteogenic pathway. On p. 6131, Ishii et al. report that the basic helix-loop-helix gene Twist and the homeobox gene Msx2 – mutations in which cause craniosynostosis (premature fusion of the skull bones) and calvarial foramina (holes in the skull vault)in humans – cooperatively control the differentiation and proliferation of skeletogenic mesenchyme in mice. They show that the calvarial foramen defect in Msx2 homozygous mutant mice is caused by fewer neural crest cells committing to osteogenesis, followed by a reduction in their proliferation. By analysing skull vault defects in Msx2-Twist double mutants, the researchers conclude that Msx2 and Twist act in parallel to direct the correct patterning of the frontal bone.