During brain development in vertebrates and invertebrates, a sheet of neuroectodermal cells transforms into a complex three-dimensional structure that contains many neural cell types. The specification of these neural cells depends on the dorsoventral (DV) patterning of the neuroectoderm. Now, on p. 3937, Seibert and colleagues describe a novel regulatory network of homeobox transcription factors that underlies DV patterning in the developing Drosophila brain. Using expression studies and loss- and gain-of-function experiments, the researchers show that the empty spiracles gene (ems) and the Nk6 homeobox gene (Nkx6) encode key regulators of the DV genetic network. Intriguingly, ems, an anteroposterior patterning gene, controls the expression of the conserved homeobox DV genes Nkx6, ventral nervous system defective (vnd), intermediate neuroblasts defective (ind) and muscle segment homeobox (msh); conversely, these DV genes control the expression of ems. The researchers also show that cross-repressive interactions between pairs of homeodomain factors establish DV gene expression domains in the fly brain, a situation that resembles that seen in developing mouse brains.