@article{3fe917018ec4400881dc156c993a9791,
title = "Optogenetic Rescue of a Patterning Mutant",
abstract = "Animal embryos are patterned by a handful of highly conserved inductive signals. Yet, in most cases, it is unknown which pattern features (i.e., spatial gradients or temporal dynamics) are required to support normal development. An ideal experiment to address this question would be to “paint” arbitrary synthetic signaling patterns on “blank canvas” embryos to dissect their requirements. Here, we demonstrate exactly this capability by combining optogenetic control of Ras/extracellular signal-related kinase (ERK) signaling with the genetic loss of the receptor tyrosine-kinase-driven terminal signaling patterning in early Drosophila embryos. Blue-light illumination at the embryonic termini for 90 min was sufficient to rescue normal development, generating viable larvae and fertile adults from an otherwise lethal terminal signaling mutant. Optogenetic rescue was possible even using a simple, all-or-none light input that reduced the gradient of Erk activity and eliminated spatiotemporal differences in terminal gap gene expression. Systematically varying illumination parameters further revealed that at least three distinct developmental programs are triggered at different signaling thresholds and that the morphogenetic movements of gastrulation are robust to a 3-fold variation in the posterior pattern width. These results open the door to controlling tissue organization with simple optical stimuli, providing new tools to probe natural developmental processes, create synthetic tissues with defined organization, or directly correct the patterning errors that underlie developmental defects.",
keywords = "Drosophila, Erk, MAP kinase, cell fate, embryogenesis, optogenetics, patterning, signal transduction",
author = "Johnson, {Heath E.} and Djabrayan, {Nareg J.V.} and Shvartsman, {Stanislav Y.} and Toettcher, {Jared E.}",
note = "Funding Information: We thank Trudi Sch{\"u}pbach and Yogesh Goyal for helpful discussions during the planning stages of our work, Romain Levayer for sharing the miniCic biosensor, Gerardo Jimenez for sharing DNA constructs used to design transcriptional reporters of tll and hkb, and Shannon Keenan for testing and characterization of the MS2 reporters lines. H.E.J. was supported by the NIH Ruth Kirschstein fellowship F32GM119297 . This work was also supported by NIH grant DP2EB024247 and NSF CAREER Award 1750663 (to J.E.T.) and NIH grant 5R01HD085870 (to S.Y.S.). We also thank Dr. Gary Laevsky and the Molecular Biology Microscopy Core, which is a Nikon Center of Excellence, for microscopy support. Stocks obtained from the Bloomington Drosophila Stock Center ( NIH P40OD018537 ) were used in this study. Funding Information: We thank Trudi Sch?pbach and Yogesh Goyal for helpful discussions during the planning stages of our work, Romain Levayer for sharing the miniCic biosensor, Gerardo Jimenez for sharing DNA constructs used to design transcriptional reporters of tll and hkb, and Shannon Keenan for testing and characterization of the MS2 reporters lines. H.E.J. was supported by the NIH Ruth Kirschstein fellowship F32GM119297. This work was also supported by NIH grant DP2EB024247 and NSF CAREER Award 1750663 (to J.E.T.) and NIH grant 5R01HD085870 (to S.Y.S.). We also thank Dr. Gary Laevsky and the Molecular Biology Microscopy Core, which is a Nikon Center of Excellence, for microscopy support. Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. H.E.J. S.Y.S. and J.E.T. conceived and designed the project and wrote the manuscript. N.J.V.D. designed and developed the tll and hkb MS2 fly strains. H.E.J. performed all experiments. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = sep,
day = "7",
doi = "10.1016/j.cub.2020.06.059",
language = "English (US)",
volume = "30",
pages = "3414--3424.e3",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "17",
}