The Eye-Specification Proteins So and Eya Form a Complex and Regulate Multiple Steps in Drosophila Eye Development

Abstract

Sine oculis (so) and eyes absent (eya) are required for Drosophila eye development and are founding members of the mammalian Six and Eya gene families. These genes have been proposed to act with eyeless (Pax6) to regulate eye development in vertebrates and invertebrates. so encodes a highly diverged homeobox transcription factor and eya encodes a novel nuclear protein. We demonstrate that So and Eya (1) regulate common steps in eye development including cell proliferation, patterning, and neuronal development; (2) synergize in inducing ectopic eyes; and (3) interact in yeast and in vitro through evolutionarily conserved domains. We propose that an So/Eya complex regulates multiple steps in eye development and functions within the context of a network of genes to specify eye tissue identity.

Development of the zebrafish inner ear

“…In the Drosophila eye disc, the pax family proteins Eyeless (Ey) and Twin of eyeless (Toy) function in a network together with the nuclear proteins Eyes Absent (Eya), Sine Oculis (So), and Dachshund (Dach), characterized by transcriptional feedback loops and protein-protein interactions. Together, these proteins perform multiple functions, including initiation and progression of the morphogenetic furrow, an apical depression that sweeps across the eye disc, and neuronal differentiation behind it (Chen et al, 1997;Pignoni et al, 1997). Homologues of all four gene families (Pax, Eya, Six, and Dach, respectively), often with several representatives of each, exist in vertebrates.…”

Wingless Signaling in Drosophila Eye Development

“…Subdivision of the disc into separate eye and antennal primordia is first apparent in the early second instar, when Eyes absent (Eya), a target of Ey, is specifically expressed at the posterior margin of the eye disc in response to signaling by the secreted molecules Hedgehog (Hh) and Decapentaplegic (Dpp) (5,18,19). Ey also activates the expression of Sine oculis (So), a homeodomain protein that interacts with Eya and acts in conjunction with it to promote eye specification (18,20,21). Finally, the DNA-binding protein Dachshund (Dac) acts downstream of these genes but can also physically interact with Eya (18,22,23).…”

“…Finally, the DNA-binding protein Dachshund (Dac) acts downstream of these genes but can also physically interact with Eya (18,22,23). Positive feedback regulation stabilizes the expression of these four genes to lock in the retinal fate (18,20,(23)(24)(25)(26).…”

“…A preproneural domain anterior to the MF is defined by the loss of Hth and the expression of Eya, So and Dac (27). Posterior to the MF, expression of Ey, Tsh and Dac is downregulated, but Eya and So are maintained and continuously required for photoreceptor differentiation (20,27,28). The early function of the interactive retinal specification and determination network thus ensures that cells anterior to the MF are already committed to become retinal tissue before they differentiate.…”

Redéploiement des gènes Six au cours de l’évolution

“…Ces quatre gènes interviennent au cours de l'étape précoce de détermination oculaire et peuvent induire, de manière synergique, la formation d'un oeil ectopique lorsqu'ils sont surexprimés dans les disques imaginaux de l'antenne ou de la patte [7][8][9]. Non seulement des boucles de régulation positive relient génétiquement ces quatre gènes, mais leur synergie fonctionnelle semble reposer sur des interactions protéiques directes entre So et Eya, d'une part, et Eya et Dac, d'autre part [10].…”