The regulatory logic of a dose-dependent developmental fate decision

In canonical developmental patterning, the embryo is exposed to gradients of signaling activators that elicit different cellular responses depending on the activator's concentration. It remains largely unknown how very low doses of an inductive signal are read out to produce potent developmental responses. Recent optogenetic studies in early Drosophila embryos show that a brief, 5-minute ERK stimulus is sufficient to rescue the development of larval tail structures. Here, we reveal components of the molecular network that produces this sensitive developmental fate response. We find that low ERK doses produce sustained Abdominal-B (Abd-B) expression. We then show that Abd-B expression is adjacent to, but non-overlapping with, two transcriptional repressors, the ERK effector Tailless (Tll) and the gap gene Giant (Gt), under a broad range of genetic and optogenetic perturbations. We detect sensitive changes to tll, Abd-B, and gt expression in response to optogenetic ERK activation and propose that ERK-to-tailless signaling mediates the effect on Abd-B and gt. The spectrum of phenotypes produced through optogenetic manipulation is thus a powerful tool for defining how robust patterning can arise from low doses of inductive signals.