In vertebrates, the formation of somites - epithelial blocks of cells that bud off in a temporally and spatially coordinated manner from the unsegmented presomitic mesoderm - precedes the correct development of the axial skeleton,skeletal muscles and dermis. On p. 4655, Mankoo et al. report that the concerted action of the homeobox genes Meox1 and Meox2 regulates several genetic pathways that are involved in somite formation, patterning and differentiation. Mice lacking Meox1activity had defects in their vertebrae and ribs, whereas mice lacking Meox2 activity showed defective differentiation and morphogenesis of the limb muscles. Mice deficient for both genes lacked an axial skeleton and had severely deficient skeletal muscles. This unexpectedly severe phenotype indicates that Meox1 and Meox2 are both required for somite epithelialisation, patterning and boundary maintenance, as well as for the normal differentiation of both sclerotome- and dermomyotome-derived cells.