Fig. 3. R8 selection and spacing. (A) Model for spacing and phase of R8. At least two factors (Scabrous and an unknown EGFR-dependent factor) are secreted from the Atonal-expressing intermediate group to establish a repressive gradient that extends outward in all directions (purple shading). In this model, ato transcription immediately anterior (left) to the intermediate group is repressed (blue inhibitory arrows) even though pre-existing ato transcript and Ato protein are still detectable. The interdigitating areas of ubiquitous Ato (dotted circles) that lie outside the repressive gradient maintain ato transcription and will become the intermediate groups of the next column, thus establishing alternate phase and spacing. (B) Regulation of Ato expression. Stage 1 Ato is controlled by the combined inputs of positively and negatively acting factors. Stage 2 Ato (intermediate groups) marks the onset of Ato autoregulation and induction of Scabrous (Sca), one of the secreted factors that establishes the repressive gradient required for R8 spacing. Sca also potentiates Notch pathway activity during lateral inhibition of stage 2 and 3 Ato. Stage 2 Ato simultaneously induces Rhomboid family members which lead to local EGFR signaling. EGFR signaling is then hypothesized to induce a second factor that contributes to the spacing gradient. This factor is thought to induce Rough (Ro) which represses ato transcription. In stage 3 (R8 equivalence group), Ato induces Sens and is repressed by the actions of both Ro and the Notch pathway. See text for further details. Modified from Baonza et al. (Baonza et al., 2001).
