Multicellularity calls for positional information. As soon as we're dealing with 2 cells and this assembly is more than 1 + 1, differentiation must follow, the first step of which is to know who's in front and who's behind, who's on top and who's underneath. By sticking to two phyla (arthropods and vertebrates), I've taken as my starting point a gene "from the front", i.e. Otx2 and its orthologs, found as early as the first metazoans, or at least already in cnidarians.
The anterior central nervous system of the fly is composed of three ganglia, proto-, deuto- and trito-cerebrum, and Otd is expressed essentially in the first two ganglia. Similarly, in mice, Otx2 is expressed from the forebrain to the border between the metencephalon and mesencephalon. Deletion of Otd in flies and Otx2 in mice leads to the same phenotype of forebrain loss. The result is an evolutionary homology (orthology) of genes that is also found at the level of expression sites and function. Indeed, if you replace Otd with mouse or human Otx2, the fly gets its head back. Hence the question: can the fly gene replace the mouse gene?
