Optogenetic rescue of a developmental patterning mutant

Abstract

Animal embryos are partitioned into spatial domains by complex patterns of signaling and gene expression, yet it is still largely unknown what features of a developmental signal are essential. Part of the challenge arises because it has been impossible to \"paint\" arbitrary signaling patterns on an embryo to test their sufficiency. Here we demonstrate exactly this capability by combining optogenetic control of Ras/Erk signaling with the genetic loss of terminal signaling in early Drosophila embryos. Simple all-or-none light inputs at the embryonic termini were able to completely rescue normal development, generating viable larvae and fertile adults from this otherwise-lethal genetic mutant. Systematically varying illumination parameters further revealed that at least three distinct developmental programs are triggered by different cumulative doses of Erk. These results open the door to the targeted design of complex morphogenetic outcomes as well as the ability to correct patterning errors that underlie developmental defects.\n\nSummarySpatial gradients of protein activity pattern all developing embryos. But which features of these patterns are essential and which are dispensable for development? Answering this question has been deceptively difficult, due to the difficulty of shaping spatial gradients using chemical or genetic perturbations. Johnson and colleagues use optogenetics to fully restore normal embryo development with a pattern of light, opening the door to complete control over spatial organization in developing and engineered tissues.