Franck Pichaud

Distinction between Color Photoreceptor Cell Fates Is Controlled by Prospero in Drosophila

The Drosophila compound eye consists of approximately 750 independently functioning ommatidia, each containing two photoreceptor subpopulations. The outer photoreceptors participate in motion detection, while the inner photoreceptors contribute to color vision. Although the inner photoreceptors, R7 and R8, terminally differentiate into functionally related cells, they differ in their molecular and morphological makeup. Our data indicates that several aspects of R7 versus R8 cell fate determination are regulated by the transcription factor Prospero (Pros). pros is specifically expressed in R7 cells, and R7 cells mutant for pros derepress R8 rhodopsins, lose R7 rhodopsins and acquire an R8-like morphology. This suggests that R7 inner photoreceptor cell fate is acquired from a default R8-like fate that is regulated, in part, via the direct transcriptional repression of R8 rhodopsins in R7 cells. Furthermore, this study provides transcriptional targets for pros that may lend insight into its role in regulating neuronal development in flies and vertebrates.

Homothorax switches function of Drosophila photoreceptors from color to polarized light sensors

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.

Otd/Crx, a Dual Regulator for the Specification of Ommatidia Subtypes in the Drosophila Retina

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.

Pax genes and eye organogenesis

Pax6 is a highly conserved gene that controls eye development in all species where it has been tested. In spite of this common master control regulator, the eyes of different animals are morphologically very different and it is believed that they have evolved independently multiple times through evolution. Recent works looking at eye development in primitive species offer some explanation as to the surprising amount of conservation in genetic and morphogenetic pathways involved in eye development. These studies not only implicate the Pax genes but also the So/Six gene family in playing a crucial ancestral role in visual system development.

homothorax and iroquois-C genes are required for the establishment of territories within the developing eye disc

In Drosophila the eye-antennal disc gives rise to most adult structures of the flys head. Yet the molecular basis for its regionalization during development is poorly understood. Here we show that homothorax is required early during development for normal eye development and is necessary for the formation of the ventral head capsule. In the ventral region of the disc only, homothorax and wingless are involved in a positive feedback loop necessary to restrict eye formation. homothorax is able to prevent the initiation and progression of the morphogenetic furrow without inducing wingless, which points to homothorax as a key negative regulator of eye development. In addition, we show that the iroquois-complex genes are required for dorsal head development antagonizing the function of homothorax in this region of the disc.

Reinventing a Common Strategy for Patterning the Eye

All together, these findings must be placed in the context of the recent realization, based on complete genome sequences, that evolution toward a higher level of complexity does not rely on the dramatic acquisition of new regulatory functions, or even on a large increase in gene number. It has become clear that Nature uses over and over again a limited number of biochemical modules, such as hh/Shh or dpp/BMP, to achieve various simple patterning tasks. It appears now that patterning of complex tissues also reuses networks of these modules simply by changing the rules of their interaction. For instance, changes in the promoters of hh and dpp as well as changes in the targets of these signaling molecules through the influence of the genes that determine the nature of the structure (master regulators) might allow the development of new structures during evolution.It is very likely that the primitive ancestral unit from which eyes evolved was simply a photoreceptive cell that used Pax6 to activate expression of an opsin. As different eyes became more complex, Pax6 became restricted to progenitor cells within the retina. Then, a convergent strategy that used the interactions between several preexisting biochemical modules such as hh, dpp, and N was superimposed onto the Pax6 module to pattern the crystalline arrays of photoreceptors (Figure 3(Figure 3). Differences between phyla in the details of the regulation of such conserved genes and networks support the idea that they have been recruited independently through evolution to elaborate new eye structures. It is striking that very complex and distinct developmental processes are achieved with a relatively restricted and simple number of interlinked genetic modules such as the hh, dpp, N, and EGFR pathways. This leads to the notion that similar strategies do not necessarily imply common ancestry of the organ, but instead reflect the reuse of an efficient mechanism invented for a similar task.

A green fluorescent protein enhancer trap screen in Drosophila photoreceptor cells

The Drosophila ommatidia contain two classes of photoreceptor cells (PRs), the outer and the inner PRs. We performed an enhancer trap screen in order to target genes specifically expressed in PRs. Using the UAS/GAL4 method with enhanced green fluorescent protein (eGFP) as a vital marker, we screened 180000 flies. Out of 2730 lines exhibiting new eGFP patterns, we focused on 16 lines expressing eGFP in particular subsets of PRs. In particular, we describe three lines inserted near the spalt major, m-spondin and furrowed genes, whose respective expression patterns resemble those genes. These genes had not been reported to be expressed in the adult eye. These examples clearly show the ability of our screen to target genes expressed in the adult Drosophila eye.

Evolution of color vision

Color vision is achieved by comparing the inputs from retinal photoreceptor neurons that differ in their wavelength sensitivity. Recent studies have elucidated the distribution and phylogeny of opsins, the family of light-sensitive molecules involved in this process. Interesting new findings suggest that animals have evolved a strategy to achieve specific sensitivity through the mutually exclusive expression of different opsin genes in photoreceptors.

A new view of photoreceptors

The light-gathering structures in our eyes are specialized membranes found on cells known as photoreceptors. Two studies show that a protein called Crumbs is crucial for the development of these membranes.