Natural variation in stochastic photoreceptor specification and color preference in Drosophila

Abstract

Each individual perceives the world in a unique way, but little is known about the genetic basis of variation in sensory perception. In the fly eye, the random mosaic of color-detecting R7 photoreceptor subtypes is determined by stochastic on/off expression of the transcription factor Spineless (Ss). In a genome-wide association study, we identified a naturally occurring insertion in a regulatory DNA element in ss that lowers the ratio of SsON to SsOFF cells. This change in photoreceptor fates shifts the innate color preference of flies from green to blue. The genetic variant increases the binding affinity for Klumpfuss (Klu), a zinc finger transcriptional repressor that regulates ss expression. Klu is expressed at intermediate levels to determine the normal ratio of SsON to SsOFF cells. Thus, binding site affinity and transcription factor levels are finely tuned to regulate stochastic expression, setting the ratio of alternative fates and ultimately determining color preference.

Altering the Temporal Regulation of One Transcription Factor Drives Evolutionary Trade-Offs between Head Sensory Organs

“…However, what feature of the two enhancer sequences causes their different temporal regulation is not known. A recent study identified a single nucleotide insertion that influences photoreceptor specification and ultimately color preference in Drosophila by modulating the affinity for a TF named Klumpfuss (Anderson et al, 2017). Together with our work, this suggests a general role for variation in suboptimal TF binding sites in sensory evolution (Crocker et al, 2016).…”

Coordination between stochastic and deterministic specification in the Drosophila visual system

“…Following matching with their R7 subtypes, controlled by Dpr11/DIPγ for yR7s/yDm8s (discussed below), supernumerary Dm8s are culled by apoptosis. Because the ratio of ommatidial subtypes can vary among individuals (Anderson et al, 2017), this mechanism allows the perfect matching that is observed in adult, where most R7s, if not all, are innervated by a single Dm8 of the proper type. This developmental plasticity provides a powerful mechanism to transmit the stochastic formation of the photoreceptor mosaic to the deterministic patterning of the brain.…”

Identification of genes involved in the differentiation of R7y and R7p photoreceptor cells inDrosophila

“…The genetic screen described here was developed to identify new genes involved in the cell fate decision that regulates Rh3 versus Rh4 expression in R7p and R7y photoreceptors cells, respectively. Three genes, ss, tgo and klu are required for this process (WERNET et al 2006;THANAWALA et al 2013;JOHNSTON AND DESPLAN 2014;ANDERSON et al 2017) and we have shown that the cell fate decision between R7p and R7y also depends upon the Epidermal growth factor receptor (Egfr) (BIRKHOLZ et al 2009a). We used the P{EP} transposable element (RORTH 1996) in a three-part screen, taking advantage of its utility in single P-element mutagenesis and as a modular GAL4 system for over-or mis-expression ( Figure 1A-B).…”

“…Two main ommatidial subtypes were identified based on pale or yellow fluorescence when illuminated with blue light (KIRSCHFELD et al 1978;FRANCESCHINI et al 1981), and contain R7pale/R8pale (R7p/R8p) or R7yellow/R8yellow (R7y/R8y) cell pairs expressing Rh3/Rh5 or Rh4/Rh6, respectively (CHOU et al 1996;PAPATSENKO et al 1997;CHOU et al 1999). The R7y and R7p photoreceptor cells are distributed randomly (BELL et al 2007) and thought to be generated stochastically through the action of spineless (ss), tango (tgo) and klumpfuss (klu) (WERNET et al 2006;THANAWALA et al 2013;JOHNSTON AND DESPLAN 2014;ANDERSON et al 2017). The hypothesis behind this stochastic cell-fate mechanism is that variation in the expression of ss in individual R7 cells in the developing pupal eye leads to the formation of R7y and R7p cells.…”