The transcription factor Pax6 has long been considered the ‘master regulator’ of eye development across evolution – ever since the discoveries that the Drosophila homolog, eyeless, can substitute for vertebrate Pax6, and that both fly and mammalian Pax6 can induce ectopic eyes. However, and despite extensive analysis of the gene regulatory network operating downstream of eyeless, we still have an incomplete understanding of how this transcription factor actually promotes eye development. Justin Kumar and colleagues now provide further insights into the role of this key protein, and propose a surprising model for the mechanism of Eyeless action. eyeless mutant alleles typically show variable phenotypes – ranging from rare no-eyed flies through to almost wild-type appearance – likely due to partial redundancy with the orthologous twin of eyeless gene. Intriguingly, however, depletion of eyeless exclusively in the peripodial epithelium that overlies the eye-antennal disc also leads to a variably penetrant eye loss phenotype. The authors show that this is due to failure of Dpp-mediated signalling to the posterior margin of the eye disc, normally required for initiation of the morphogenetic furrow and hence differentiation. Thus, while the assumption had been that Eyeless would play an autonomous role within the eye disc, these data rather suggest that it exerts its activity at least partially non-autonomously – somewhat analogous to vertebrate Pax6, expression of which in the lens regulates retinal development.
