Dynamics of an incoherent feedforward loop drive ERK-dependent pattern formation in the early Drosophila embryo

Abstract

<p>Positional information in development often manifests as stripes of gene expression, but how stripes form remains incompletely understood. Here, we use optogenetics and live-cell biosensors to investigate the posterior <em>brachyenteron</em> (<em>byn</em>) stripe in early <em>Drosophila</em> embryos. This stripe depends on interpretation of an upstream ERK activity gradient and the expression of two target genes, <em>tailless</em> (<em>tll</em>) and <em>huckebein</em> (<em>hkb</em>), that exert antagonistic control over <em>byn</em>. We find that high or low doses of ERK signaling produce transient or sustained <em>byn</em> expression, respectively. Although <em>tll</em> transcription is always rapidly induced, <em>hkb</em> converts graded ERK inputs into a variable time delay. Nuclei thus interpret ERK amplitude through the relative timing of <em>tll</em> and <em>hkb</em> transcription. Antagonistic regulatory paths acting on different timescales are hallmarks of an incoherent feedforward loop, which is sufficient to explain <em>byn</em> dynamics and adds temporal complexity to the steady-state model of <em>byn</em> stripe formation. We further show that ‘blurring’ of an all-or-none stimulus through intracellular diffusion non-locally produces a <em>byn</em> stripe. Overall, we provide a blueprint for using optogenetics to dissect developmental signal interpretation in space and time.<br></p>