We employed robotic methods and the whole-genome sequence of Drosophila melanogaster to facilitate a large-scale expression screen for spatially restricted transcripts in Drosophila embryos. In this screen, we identified a pair of genes, scylla (scyl) and charybde (chrb), that code for dorsal transcripts in early Drosophila embryos and are homologous to the human apoptotic gene RTP801. In Drosophila, both gene products are transcriptionally regulated targets of Dpp/Zen-mediated signal transduction and appear more generally to be downstream targets of homeobox regulation. Gene disruption studies revealed the functional redundancy of scyl and chrb, as well as their requirement for embryonic head involution. From the perspective of functional genomics, our studies demonstrate that global surveys of gene expression can complement traditional genetic screening methods for the identification of genes essential for development: beginning from their spatio-temporal expression profiles and extending to their downstream placement relative to dpp and zen, our studies reveal roles for the scyl and chrb gene products as links between patterning and cell death.