title: The Spatiotemporal Limits of Developmental Erk Signaling.
abstract: Animal development is characterized by signaling events that occur at precise locations and times within the embryo, but determining when and where such precision is needed for proper embryogenesis has been a long-standing challenge. Here we address this question for extracellular signal regulated kinase (Erk) signaling, a key developmental patterning cue. We describe an optogenetic system for activating Erk with high spatiotemporal precision in vivo. Implementing this system in Drosophila, we find that embryogenesis is remarkably robust to ectopic Erk signaling, except from 1 to 4 hr post-fertilization, when perturbing the spatial extent of Erk pathway activation leads to dramatic disruptions of patterning and morphogenesis. Later in development, the effects of ectopic signaling are buffered, at least in part, by combinatorial mechanisms. Our approach can be used to systematically probe the differential contributions of the Ras/Erk pathway and concurrent signals, leading to a more quantitative understanding of developmental signaling.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Heath E
authors.initials: HE
authors.lastname: Johnson
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Goyal
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Pannucci
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Trudi
authors.initials: T
authors.lastname: Schüpbach
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Stanislav Y
authors.initials: SY
authors.lastname: Shvartsman
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address: toettcher@princeton.edu.
authors.forename: Jared E
authors.initials: JE
authors.lastname: Toettcher
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000196:embryology* / Q000201:enzymology* / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics / Q000528:radiation effects; D004789:Enzyme Activation / Q000528:radiation effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000528:radiation effects; D008027:Light; D020935:MAP Kinase Signaling System; D062308:Optogenetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000528:radiation effects; D018631:ras Proteins / Q000378:metabolism
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins
keywords: Drosophila; MAP kinase; embryogenesis; optogenetics; signal transduction