twin of eyeless, a Second Pax-6 Gene of Drosophila, Acts Upstream of eyeless in the Control of Eye Development

Abstract

The Drosophila Pax-6 gene eyeless (ey) plays a key role in eye development. Here we show tht Drosophila contains a second Pax-6 gene, twin of eyeless (toy), due to a duplication during insect evolution. Toy is more similar to vertebrate Pax-6 proteins than Ey with regard to overall sequence conservation, DNA-binding function, and early expression in the embryo, toy and ey share a similar expression pattern in the developing visual system, and targeted expression of Toy, like Ey, induces the formation of ectopic eyes. Genetic and biochemical evidence indicates, however, that Toy functions upstream of ey by directly regulating the eye-specific enhancer of ey. Toy is therefore required for initiation of ey expression in the embryo and acts through Ey to activate the eye developmental program.

Growth and specification of the eye are controlled independently by Eyegone and Eyeless in Drosophila melanogaster

“…To test this hypothesis, we assayed the eye-growth capability of flies expressing each Pax6 protein, including Eyg and the novel Eyg-like protein (Toe) encoded by the gene twin of eyegone (toe; also known as CG10704), identified by the Berkeley Drosophila Genome Project. Using ey-GAL4-mediated expression of UAS-regulated Pax transgenes 27,28,37,38 , we compared the eye size of flies coexpressing the Pax proteins and Fng with that of flies expressing Fng alone.…”

“…The gene eyeless (ey) 26 and its paralog twin of eyeless (toy) 27 encode canonical Pax6 products (Ey and Toy, respectively) and are the key players in the specification of eye identity. Ey and Toy trigger ectopic eyes when misexpressed 27,28 .…”

“…Ey and Toy trigger ectopic eyes when misexpressed 27,28 . Mouse Pax6 can substitute for D. melanogaster Ey in the formation of ectopic eyes 28 , and D. melanogaster Ey or Toy can induce vertebrate-type eyes in the frog embryo 29 .…”

Wingless Signaling in Drosophila Eye Development

“…The two Pax6 homologues toy and ey act at the top of the cascade, with toy upstream of ey; both are necessary and sufficient for eye development but are also required for formation of the entire head, reflecting their early expression in the antennal disc (2,3,17,18). 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).…”

“…The adult eye and head capsule develop from an epithelial bilayer known as the eye-antennal imaginal disc. This structure derives from a primordial group of about 20 cells determined early during embryogenesis by expression of the Pax6 transcription factors Twin of eyeless (Toy) and Eyeless (Ey) (2,3). The disc invaginates from the embryonic ectoderm and grows by asynchronous cell divisions until the third larval instar (1,4).…”