Two-step selection of a single R8 photoreceptor: a bistable loop betweensenselessandroughlocks in R8 fate

Abstract

Patterning of sensory organs requires precise regulation of neural induction and repression. The neurocrystalline pattern of the adult Drosophila compound eye is generated by ordered selection of single founder photoreceptors (R8s) for each unit eye or ommatidium. R8 selection requires mechanisms that restrict R8 potential to a single cell from within a group of cells expressing the proneural gene atonal (ato). One model of R8 selection suggests that R8 precursors are selected from a three-cell ‘R8 equivalence group’ through repression of ato by the homeodomain transcription factor Rough (Ro). A second model proposes that lateral inhibition is sufficient to select a single R8 from an equipotent group of cells called the intermediate group (IG). Here, we provide new evidence that lateral inhibition, but not ro, is required for the initial selection of a single R8 precursor. We show that in ro mutants, ectopic R8s develop from R2,5 photoreceptor precursors independently of ectopic Ato and hours after normal R8s are specified. We also show that Ro directly represses the R8 specific zinc-finger transcription factor senseless (sens) in the developing R2,5 precursors to block ectopic R8 differentiation. Our results support a new model for R8 selection in which lateral inhibition establishes a transient pattern of selected R8s that is permanently reinforced by a repressive bistable loop between sens and ro. This model provides new insight into the strategies that allow successful integration of a repressive patterning signal, such as lateral inhibition, with continued developmental plasticity during retinal differentiation.

Does Unc–GFP uncover ciliary structures in the rhabdomeric eye of Drosophila?

“…Interestingly, the localization of Unc-GFP is consistent with the behaviour of R8, the first differentiating rhabdomeric cell that plays a pivotal role in the ommatidia assembly (Frankfort and Mardon, 2002;Pepple et al, 2008). The Unc-GFP signal indeed first appears in the more posterior cell of the arc-like clusters at the beginning of ommatidia formation.…”

A dynamical model of ommatidial crystal formation

“…Because the cells of the eye disc are not packed in an ordered lattice at this stage (32), sometimes the template allows two R8 candidates to be induced almost simultaneously; both then reach the R8 state before either can repress the other. Even the best parameter sets in our model lead to a low frequency of such R8 twinning; interestingly, twinned R8s are indeed observed experimentally posterior to the resolving IGs in ∼6% of ommatidia (33). That twins always resolve in wild-type discs, but not in our model, likely indicates some slower, ancillary inhibitory process in vivo (SI Text).…”

dEHBP1 regulates Scabrous secretion during Notch mediated lateral inhibition

“…2G-I), an E3 ubiquitin ligase that is necessary for the internalization of the ligand Dl and its ability to signal to the Notch receptor (Lai et al, 2001;Lai and Rubin, 2001a;Lai and Rubin, 2001b;Le Borgne and Schweisguth, 2003;Li and Baker, 2001;Pavlopoulos et al, 2001). On the basis of this observation, we determined whether signaling pathways other than Notch may contribute to the development of supernumerary R8 photoreceptors based on known mutants, including loss of Ecadherin (Mirkovic and Mlodzik, 2006), loss of Rough (Pepple et al, 2008) or aberrant EGFR signaling (Rawlins et al, 2003;Spencer and Cagan, 2003). However, expression of E-cadherin, Rough, as well as dpERK and pointed-LacZ are not altered in dEHBP1 mutant clones (supplementary material Fig.…”