Stochastic spineless expression creates the retinal mosaic for colour vision

Abstract

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...

Nedd9/Hef1/Cas-L mediates the effects of environmental pollutants on cell migration and plasticity

“…It is unclear at this stage whether dioxin and the human AhR would activate in vivo cell migration under any physiological or pathological conditions. In this regard, it is interesting to note that the invertebrate Ahr, specifically in Caenorhabditis elegans and Drosophila, does not seem to mediate response to xenobiotics but is rather at least partially implicated in determining neuronal fate and migration, which is in line with our observations (Crews and Brenman, 2006;Qin et al, 2006;Wernet et al, 2006;McMillan and Bradfield, 2007). Studies of rodent AhR lead to a more balanced view of its functions (McMillan and Bradfield, 2007).…”

A genetic timer through noise-induced stabilization of an unstable state

“…Noise within genetic circuits is therefore thought to contribute to phenotypic heterogeneity in genetically identical cellular populations. It has also recently been shown experimentally that noise can trigger cellular differentiation in fruit flies and bacteria (14,17,18,24). Together, these studies establish that noise can play an active functional role in cellular processes by effectively destabilizing and thus inducing escape from stable phenotypic states.…”

Variability in β-catenin pulse dynamics in a stochastic cell fate decision inC. elegans

“…1a) (Gamba et al, 2015;Wernet et al, 2006). Currently, it is not known if and where in the signaling network that controls the Hyp7/fusion versus VPC fate decision such a bimodal distribution arises.…”

“…One striking example, conserved in development from Drosophila to humans, is the stochastic choice of photoreceptor cells in the retina to cell-autonomously select to express only one photopigment from a total of three photopigments, with each stochastically picked at a defined frequency (Roorda and Williams, 1999;Smallwood et al, 2002). Using Drosophila as a model system, stochastic expression of a transcription factor, Spineless (Ss), was identified as the mechanism for the stochastic photopigment selection, since high levels of Ss expression correlated with the frequency of a particular fate, while cells with lower levels of Ss correlated with the alternative cell fate, indicating the cell fate choice occurs by the creation of bimodality in the level of the spineless expression (Wernet et al, 2006). How the bimodality arose upstream in the genetic network and what sources of noise or variability could be responsible for variable expression still remains a question.…”