Drosophila colour vision is achieved by R7 and R8 photoreceptor cells present in every ommatidium. The fly retina contains two types of ommatidia, called 'pale' and 'yellow', defined by different rhodopsin pairs expressed in R7 and R8 cells. Similar to the human cone photoreceptors, these ommatidial subtypes are distributed stochastically in the retina. The choice between pale versus yellow ommatidia is made in R7 cells, which then impose their fate onto R8. Here we report that the Drosophila dioxin receptor Spineless is both necessary and sufficient for the formation of the ommatidial mosaic. A short burst of spineless expression at mid-pupation in a large subset of R7 cells precedes rhodopsin expression. In spineless mutants, all R7 and most R8 cells adopt the pale fate, whereas overexpression of spineless is sufficient to induce the yellow R7 fate. Therefore, this study suggests that the entire retinal mosaic required for colour vision is defined by the stochastic expression of a single transcription factor, Spineless.The ability to discriminate between colours has evolved independently in vertebrates and invertebrates 1,2 . However, despite the obvious differences in eye development and design, both flies and humans have developed retinal mosaics where classes of photoreceptor cells (PRs) with different spectral sensitivity are randomly distributed 3,4 . The compound eye of Drosophila consists of ,800 optical units (ommatidia), each containing eight PRs in addition to accessory cells 5 . In each ommatidium, the six 'outer PRs' (R1-R6) function like the vertebrate rod cells, as they are required for motion detection in dim light 6,7 . These cells express the broad-spectrum rhodopsin, Rh1 (ref. 8). The 'inner PRs' (R7 and R8) may be viewed as the equivalent of the colour-sensitive vertebrate cone cells, which express a range of different rhodopsin molecules 9-13 .Ommatidial subset specification in Drosophila The general rule of sensory receptor exclusion also applies to Drosophila ommatidia, where only one rhodopsin gene is expressed by a given PR 14 . The expression of inner PR rhodopsins can be used to distinguish three ommatidial subtypes 15,16 ( Supplementary Fig. 1a, b). Two of the subtypes are distributed randomly throughout the retina: ,30% of ommatidia express ultraviolet-sensitive Rh3 in R7 cells and blue-sensitive Rh5 in R8 cells, and therefore are specialized in the detection of short wavelengths ('pale' ommatidia, p; Fig. 1a, blue). The remaining ,70% express another ultraviolet-sensitive opsin (Rh4) in R7 and green-sensitive Rh6 in R8, making them more responsive to longer wavelengths ('yellow' ommatidia, y; Fig. 1a, yellow). The coupled expression of Rh3/Rh5 or Rh4/Rh6 within the same ommatidium results from communication between R7 and R8 ( Supplementary Fig. 1b, c). In the dorsal rim area (DRA) (Fig. 1a, pink), a third type of ommatidia exists 17 in which both R7 and R8 express ultraviolet-sensitive Rh3 (refs 18, 19). These ommatidia are used to detect the e-vector of polarized sunlight for or...

Different classes of photoreceptors (PRs) allow animals to perceive various types of visual information. In the Drosophila eye, the outer PRs of each ommatidium are involved in motion detection while the inner PRs mediate color vision. In addition, flies use a specialized class of inner PRs in the "dorsal rim area" of the eye (DRA) to detect the e-vector of polarized light, allowing them to exploit skylight polarization for orientation. We show that homothorax is both necessary and sufficient for inner PRs to adopt the polarization-sensitive DRA fate instead of the color-sensitive default state. Homothorax increases rhabdomere size and uncouples R7-R8 communication to allow both cells to express the same opsin rather than different ones as required for color vision. Homothorax expression is induced by the iroquois complex and the wingless (wg) pathway. However, crucial wg pathway components are not required, suggesting that additional signals are involved.

Color vision in Drosophila relies on the comparison between two color-sensitive photoreceptors, R7 and R8. Two types of ommatidia in which R7 and R8 contain different rhodopsins are distributed stochastically in the retina and appear to discriminate short (p-subset) or long wavelengths (y-subset). The choice between p and y fates is made in R7, which then instructs R8 to follow the corresponding fate, thus leading to a tight coupling between rhodopsins expressed in R7 and R8. Here, we show that warts, encoding large tumor suppressor (Lats) and melted encoding a PH-domain protein, play opposite roles in defining the yR 8 or pR8 fates. By interacting antagonistically at the transcriptional level, they form a bistable loop that insures a robust commitment of R8 to a single fate, without allowing ambiguity. This represents an unexpected postmitotic role for genes controlling cell proliferation (warts and its partner hippo and salvador) and cell growth (melted).

Comparison between the inputs of photoreceptors with different spectral sensitivities is required for color vision. In Drosophila, this is achieved in each ommatidium by the inner photoreceptors R7 and R8. Two classes of ommatidia are distributed stochastically in the retina: 30% contain UV-Rh3 in R7 and blue-Rh5 in R8, while the remaining 70% contain UV-Rh4 in R7 and green-Rh6 in R8. We show here that the distinction between the rhodopsins expressed in the two classes of ommatidia depends on a series of highly conserved homeodomain binding sites present in the rhodopsin promoters. The homeoprotein Orthodenticle acts through these sites to activate rh3 and rh5 in their specific ommatidial subclass and through the same sites to prevent rh6 expression in outer photoreceptors. Therefore, Otd is a key player in the terminal differentiation of subtypes of photoreceptors by regulating rhodopsin expression, a function reminiscent of the role of one of its mammalian homologs, Crx, in eye development.

Most important, certain carotenoids are the precursors (provitamins) for the formation of vitamin A in animals. This vitamin is needed for vision in the entire animal kingdom. The visual pigments (rhodopsins) of animals are composed of a retinoid chromophore (vitamin A derivative) bound to a protein moiety (opsin) embedded in the photoreceptor membranes (3, 4). Light activation of the visual pigments triggers a G protein-coupled receptor cascade leading to changes in the permeability of the photoreceptor cell membranes. Besides being crucial for vision, in vertebrates vitamin A is also important in development and cellular differentiation processes. Here, the vitamin A derivative retinoic acid, together with its nuclear receptors, is involved in the regulation of diverse target genes; consequently, complete vitamin A deficiency leads to early embryonic death (5).To become biologically active, dietary carotenoids must first be absorbed, then delivered to the site of action in the body and, in the case of provitamin A function, metabolically converted. Despite the general importance of carotenoids in animals, their metabolism is still poorly understood (6). Invertebrates like Drosophila represent excellent models for the genetic dissection of the pathway leading from dietary carotenoids to vitamin A. Here, this vitamin is only needed for vision; therefore, its deficiency has no fatal consequences. Among the various Drosophila mutants affected in their visual performance (4), the two mutants ninaB and ninaD lack the visual chromophore of the fly, 3-hydroxyretinal, when raised on standard media with carotenoids as the sole source for vitamin A formation (7). By analyzing the molecular basis of the blindness of ninaB mutants, we already showed that the phenotype is caused by mutations in a gene coding a carotene-15,15Ј-oxygenase and molecularly identified the key enzyme for carotenoid conversion to vitamin A in animals (8, 9). By sequence identity, orthologs to this insect gene were cloned from several vertebrate species including man, showing that the enzymes catalyzing vitamin A formation are evolutionarily well conserved (10-13). In Drosophila, mRNA expression of ninaB was exclusively found in the head, in agreement with retinoids being restricted in their distribution to the eyes (8,14). In vertebrates (with vitamin A needed also for cellular differentiation processes), the vitamin A-forming enzyme is expressed in a variety of different tissues including reproductive tissues and the eyes (10, 12, 13). After dietary absorption, carotenoids must be distributed to these tissues to be converted to vitamin A.In the second chromophore-less Drosophila mutant, ninaD, the carotenoid content was shown to be specifically and significantly altered compared with wild-type (wt) flies and was ineffective at mediating visual pigment synthesis (14). This phenotype is presumably caused by a defect in the body distribution of dietary carotenoids and makes the ninaD gene an interesting candidate for a molecular player necessary for ...

SUMMARY Background Linearly polarized light originates from atmospheric scattering, or surface reflections, and is perceived by, insects, spiders, cephalopods crustaceans and some vertebrates. Thus, the neural basis underlying how this fundamental quality of light is detected is of broad interest. Morphologically unique, polarization-sensitive ommatidia exist in the dorsal periphery of many insect retinas, forming the ‘Dorsal Rim Area’ (DRA). However, much less is known about the retinal substrates of behavioral responses to polarized reflections. Summary Drosophila exhibits polarotactic behavior, spontaneously aligning with the e-vector of linearly polarized light, when stimuli are presented either dorsally or ventrally. By combining behavioral experiments with genetic dissection and ultrastructural analyses, we show that distinct photoreceptors mediate the two behaviors: inner photoreceptors R7+R8 of DRA ommatidia are necessary and sufficient for dorsal polarotaxis, whereas ventral responses are mediated by combinations of outer and inner photoreceptors, both of which manifest previously unknown features that render them polarization-sensitive. Conclusions Drosophila uses separate retinal pathways for the detection of linearly polarized light emanating from the sky, or from shiny surfaces. This work establishes a behavioral paradigm that will enable genetic dissection of the circuits underlying polarization vision.

The genome versus experience dichotomy has dominated understanding of behavioral individuality. By contrast, the role of nonheritable noise during brain development in behavioral variation is understudied. Using Drosophila melanogaster, we demonstrate a link between stochastic variation in brain wiring and behavioral individuality. A visual system circuit called the dorsal cluster neurons (DCN) shows nonheritable, interindividual variation in right/left wiring asymmetry and controls object orientation in freely walking flies. We show that DCN wiring asymmetry instructs an individual’s object responses: The greater the asymmetry, the better the individual orients toward a visual object. Silencing DCNs abolishes correlations between anatomy and behavior, whereas inducing DCN asymmetry suffices to improve object responses.

The Drosophila eye is a mosaic that results from the stochastic distribution of two ommatidial subtypes. Pale and yellow ommatidia can be distinguished by the expression of distinct rhodopsins and other pigments in their inner photoreceptors (R7 and R8), which are implicated in color vision. The pale subtype contains ultraviolet (UV)-absorbing Rh3 in R7 and blue-absorbing Rh5 in R8. The yellow subtype contains UV-absorbing Rh4 in R7 and green-absorbing Rh6 in R8. The exclusive expression of one rhodopsin per photoreceptor is a widespread phenomenon, although exceptions exist. The mechanisms leading to the exclusive expression or to co-expression of sensory receptors are currently not known. We describe a new class of ommatidia that co-express rh3 and rh4 in R7, but maintain normal exclusion between rh5 and rh6 in R8. These ommatidia, which are localized in the dorsal eye, result from the expansion of rh3 into the yellow-R7 subtype. Genes from the Iroquois Complex (Iro-C) are necessary and sufficient to induce co-expression in yR7. Iro-C genes allow photoreceptors to break the “one receptor–one neuron” rule, leading to a novel subtype of broad-spectrum UV- and green-sensitive ommatidia.