Many mesodermal cell types, including pharynx and body muscle cells, are derived from a single cell, the MS blastomere, in Caenorhabditis elegans. Mesoderm specification involves the activation of the T-box factor gene tbx-35; tbx-35 mutation results in a severe decrease in MS-derived tissue. On p. 2735, Morris Maduro and co-workers now identify the NK-2 homeobox gene ceh-51 as a novel regulator of mesoderm development. The researchers report that ceh-51 is expressed in mesoderm cells and is a direct target of TBX-35. Its overexpression causes embryonic arrest and promotes MS-derived tissue specification, whereas a null mutation results in larval arrest and pharyngeal defects. Embryos with loss-of-function mutations in both ceh-51 and tbx-35 have a more severe phenotype than do single mutants, indicating that the functions of TBX-35 and CEH-51 in mesoderm development partially overlap. Given that T-box and NK-2 factors are also crucial for heart development in flies and vertebrates, their role in regulating mesoderm development might be evolutionarily conserved.