Disease relevance of ey

• The finding that ey of Drosophila, Small eye of the mouse, and human Aniridia are encoded by homologous genes suggests that eye morphogenesis is under similar genetic control in both vertebrates and insects, in spite of the large differences in eye morphology and mode of development [1].

Psychiatry related information on ey

• Furthermore, severe defects in adult brain structures essential for vision, olfaction, and for the coordination of locomotion are provoked by two newly isolated mutations of Pax-6/eyeless that result in truncated proteins [2].
• In addition, so1 (eyeless) mutant flies show the presence of a single evening locomotor activity peak during the whole circadian day, suggesting that in wild type flies the morning and evening activity peaks may be under separate control [3].
• Brief heating of the oocytes and larvae of eyeless mutants during the critical periods of faceted-eye development caused an increase in the thermal sensitivity of the eye rudiments, which led to an increase in the number of one-eyed individuals among the flies that hatched [4].

High impact information on ey

• These results imply that ey does not induce the entire eye morphogenetic program but rather modifies ato-dependent neuronal development [5].
• The eyeless, dachshund, and eyes absent genes encode conserved, nuclear proteins that are essential for eye development in Drosophila [6].
• 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 [7].
• Pax-6 is a member of the Pax gene class and encodes a protein containing a paired domain and a homeodomain [8].
• The molecular characterization of Pax-6 genes from species of different animal phyla and the analysis of Pax-6 function in the developing eyes and central nervous system of vertebrates, Drosophila melanogaster, and Caenorhabditis elegans suggest that Pax-6 homologues share conserved functions [8].

Biological context of ey

• They are all conserved between vertebrates and insects and they interact in a combinatorial and hierarchical network to regulate each other expression. so has been shown to be directly regulated by ey through an eye-specific enhancer (so10) [9].
• We further studied the regulation of this element and found that both Drosophila Pax6 proteins namely EY and TOY bind and positively regulate so10 expression through different binding sites [9].
• Thus, eya-1 appears to play a partially redundant role with pax-6 during C. elegans embryogenesis [10].
• However, this genetic network has been used in a novel developmental context, myogenesis rather than eye development, and has been expanded to include gene family members that are not directly homologous, for example Pax3 instead of Pax6 [11].
• Using the emerging consensus sequence for SO-DNA binding we performed a genome-wide search and have thereby been able to identify eyeless as well as the signalling gene hedgehog as putative targets of so [12].

Anatomical context of ey

• Mutations of ey completely disrupted the MB neuropils, and a null mutation of dac resulted in marked disruption and aberrant axonal projections [13].
• Genetic control of development of the mushroom bodies, the associative learning centers in the Drosophila brain, by the eyeless, twin of eyeless, and Dachshund genes [13].
• The tiny rudiments of the optic lobes in eyeless double mutants still contain tangential neurons of the medulla and of the lobula complex [14].
• Therefore, in addition to performing a global photoreceptor-specific function, RCSI also appears to mediate the combined action of Pax6 and other factors and to contribute to rh regulation in subsets of photoreceptors [15].
• It is required for development of the central nervous system, and is mutated in human aniridia, mouse and rat small eye and Drosophila eyeless [16].

Physical interactions of ey

• To overcome the lack of high-quality consensus binding site sequences, phylogenetic shadowing of known Ey binding sites in sine oculis (so) was used to construct a position weight matrix (PWM) of the Ey protein [17].

Regulatory relationships of ey

• Previous work in our laboratory identified an eye/ocellus specific enhancer of the sine oculis gene that is directly regulated by eyeless and twin of eyeless [12].
• The Drosophila homeobox gene optix is capable of inducing ectopic eyes by an eyeless-independent mechanism [18].
• These results suggest that Pax-6/Ey directly regulates rhodopsin 1 gene expression by binding to the conserved P3/RCS1 element in the promoter [19].
• Here we show that Notch signaling regulates the expression of the master control genes eyeless, vestigial, and Distal-less, which in combination with homeotic genes induce the formation of eyes, wings, antennae, and legs [20].

Other interactions of ey

• Combinatorial control of Drosophila eye development by eyeless, homothorax, and teashirt [21].
• Evidence for a direct functional antagonism of the selector genes proboscipedia and eyeless in Drosophila head development [22].
• Differential interactions of eyeless and twin of eyeless with the sine oculis enhancer [9].
• Initial analysis reveals three genes, eyes absent, shifted, and Optix, as novel direct targets of Ey [17].
• We also compare the expression of Ey with that of a putative antennal specifying gene Distal-less (Dll) [23].

Analytical, diagnostic and therapeutic context of ey

• In parallel, microarray analysis of wild-type versus ectopic ey-expressing tissue, followed by microarray-based epistasis experiments in an atonal (ato) mutant background, identified 188 genes induced by ey [17].
• We used two different Drosophila full-genome DNA microarrays to compare gene expression in wild-type leg discs versus leg discs where eyeless, one of the two Drosophila Pax-6 genes, was ectopically expressed [24].
• The results of protein, phospholipid and enzyme analyses were corroborated by analyses by 'genetic dissection' using an eyeless mutant line [25].
• On a Western blot, the antibody recognizes a 41 kDa protein that is present in the heads of yellow white flies, but not in the heads of eyeless mutant flies, eyes absent [26].

References