The transcription factor glass links eye field specification with photoreceptor differentiation in Drosophila

Abstract

Eye development requires an evolutionarily conserved group of transcription factors, termed the retinal determination network (RDN). However, little is known about the molecular mechanism by which the RDN instructs cells to differentiate into photoreceptors. We show that photoreceptor cell identity in Drosophila is critically regulated by the transcription factor Glass, which is primarily expressed in photoreceptors and whose role in this process was previously unknown. Glass is both required and sufficient for the expression of phototransduction proteins. Our results demonstrate that the RDN member Sine oculis directly activates glass expression, and that Glass activates the expression of the transcription factors Hazy and Otd. We identified hazy as a direct target of Glass. Induced expression of Hazy in the retina partially rescues the glass mutant phenotype. Together, our results provide a transcriptional link between eye field specification and photoreceptor differentiation in Drosophila, placing Glass at a central position in this developmental process.

Successive requirement of Glass and Hazy for photoreceptor specification and maintenance inDrosophila

“…In contrast, the expression of Hazy starts later during pupation, after all PRs have been specified 3,13 . We and others have shown that the expression of a hazy(wt)-GFP reporter in compound eye PRs depends on Glass binding to 2 sites in the hazy promoter 9,12 . In addition to the compound eye, flies also have PRs in the ocelli (3 separate eyes located at the top of the adult head) and in the larval eye, also termed Bolwig's organ.…”

“…In addition to the compound eye, flies also have PRs in the ocelli (3 separate eyes located at the top of the adult head) and in the larval eye, also termed Bolwig's organ. Since both Glass and Hazy also play a role in the development of these organs, 9,11 , 14,16-19 we hypothesized that Glass might similarly activate hazy in PRs outside the compound eye.…”

“…Similarly, ectopic expression of Hazy can only induce a subset of phototransduction components. However, when co-expressed, Glass and Hazy can ectopically induce most of the phototransduction cascade, suggesting that both Glass and Hazy act synergistically during PR development 9 . Thus, the combinatorial action of these 2 transcription factors appears to play a central role in directing PR precursors toward a terminal differentiation program.…”

“…Together with previous results, our data suggest that Glass and Hazy are required for different tasks and at different steps in PR development. During early eye development, Glass contributes to specifying PR identity 9-12 . Later, during terminal differentiation, both Glass and Hazy activate genes that are required for the maturation of functional PRs 9,12 , 13 .…”

“…During early eye development, Glass contributes to specifying PR identity 9-12 . Later, during terminal differentiation, both Glass and Hazy activate genes that are required for the maturation of functional PRs 9,12 , 13 . Finally, Hazy is required for maintaining expression of phototransduction genes, and thus ensures the continued functionality of adult PRs.…”