Otx2, a paired-type homeobox gene, plays a vital role during embryonic rostral head development in vertebrates but regulation of its expression is poorly understood. On p. 57, Kimura-Yoshida et al. describe the embryonic expression pattern of Fotx2, the pufferfish Otx2 gene. Then, taking advantage of the small size of the Fotx2 gene compared with Otx2, the researchers surveyed the entire Fotx2 genomic region for cis-acting regulators by examining expression of a lacZ reporter linked to different Fotx2fragments in transgenic mice. They identified seven independent cis-regulators that mediated lacZ expression in spatiotemporally non-overlapping subdomains of the developing rostral head. Two of these regulators were also tested and found to work in zebrafish embryos. The researchers conclude that multiple cis-regulators in the Otx2 promoter are required to control the highly coordinated processes that occur during vertebrate head development.