title: Paused Pol II coordinates tissue morphogenesis in the Drosophila embryo.
abstract: Paused RNA polymerase (Pol II) is a pervasive feature of Drosophila embryos and mammalian stem cells, but its role in development is uncertain. Here, we demonstrate that a spectrum of paused Pol II determines the "time to synchrony"-the time required to achieve coordinated gene expression across the cells of a tissue. To determine whether synchronous patterns of gene activation are significant in development, we manipulated the timing of snail expression, which controls the coordinated invagination of ∼1,000 mesoderm cells during gastrulation. Replacement of the strongly paused snail promoter with moderately paused or nonpaused promoters causes stochastic activation of snail expression and increased variability of mesoderm invagination. Computational modeling of the dorsal-ventral patterning network recapitulates these variable and bistable gastrulation profiles and emphasizes the importance of timing of gene activation in development. We conclude that paused Pol II and transcriptional synchrony are essential for coordinating cell behavior during morphogenesis.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Mounia
authors.initials: M
authors.lastname: Lagha
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Bothma
authors.forename: Emilia
authors.initials: E
authors.lastname: Esposito
authors.forename: Samuel
authors.initials: S
authors.lastname: Ng
authors.forename: Laura
authors.initials: L
authors.lastname: Stefanik
authors.forename: Chiahao
authors.initials: C
authors.lastname: Tsui
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Johnston
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: David S
authors.initials: DS
authors.lastname: Gilmour
authors.forename: Julia
authors.initials: J
authors.lastname: Zeitlinger
authors.forename: Michael S
authors.initials: MS
authors.lastname: Levine
mesh_terms: D000818:Animals; D001483:Base Sequence; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology* / Q000201:enzymology / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D054262:Gastrulation; D018507:Gene Expression Regulation, Developmental; D008954:Models, Biological; D008969:Molecular Sequence Data; D009024:Morphogenesis; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D029721:Drosophila Proteins; C064196:dpp protein, Drosophila; D012319:RNA Polymerase II