In sea urchin embryogenesis, large blastomeres, called micromeres, and their progeny act as an important signalling centre and give rise to mesenchymal skeleton-forming cells. Ettensohn et al. have now identified a new and essential component of the gene network that controls micromere specification – Alx1, the first known invertebrate member of the Cart1/Alx3/Alx4 family of vertebrate paired-class homeodomain proteins that function in limb and craniofacial skeletal development. Morpholino knockdown and gene expression experiments show that Alx1 controls genes required for epithelial-mesenchymal transition and biomineralization. Importantly, these findings, on p. 2917, hint at an evolutionary link between certain features of skeletal development in vertebrates and sea urchins, and indicate that the ancestral deuterostome from which they derive might have had a mesenchymal cell lineage that engaged in biomineralization, in which an Alx1-like protein functioned.