The regulatory logic of a dose-dependent developmental fate decision

Abstract

In canonical developmental patterning, the embryo is exposed to gradients of signaling activators that elicit different cellular responses depending on the activators concentration. Recent optogenetic studies of terminal ERK signaling downstream of Torso receptor tyrosine kinase in the early Drosophila embryo reveal that even 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 defines this sensitive developmental fate response. We find that low ERK doses produce sustained Abdominal-B (Abd-B) expression comparable to that of wild-type embryos. Abd-B expression is adjacent to, but non-overlapping with, two other transcriptional repressors: the ERK effector Tailless (Tll) and the gap gene Giant (Gt). Analysis of gene expression patterns in response to optogenetic perturbations suggests that the Tll-dependent repression of gt constitutes the sensitive ERK-responsive step: even low tll expression leads to potent repression of gt in nearby regions, with Abd-B expression arising in a stripe between the tll and gt domains. Our work suggests that the spectrum of phenotypes produced through optogenetic manipulation can be used to define how robust patterning can arise from low doses of inductive signals. HighlightsO_LIA very low dose of receptor tyrosine kinase signaling in the early embryo induces tail formation many hours later. C_LIO_LITransient ERK activity results in stable Abd-B expression, beginning as a stripe in nuclear cycle 14. C_LIO_LIOptogenetic ERK inputs induce a spectrum of ectopic phenotypes that reveal mutually exclusive expression of Tailless, Giant, and Abd-B in the posterior. C_LIO_LITailless-dependent repression of giant is the sensitive ERK-responsive step. C_LI