XPaused Pol II coordinates tissue morphogenesis in the drosophila embryo

Mounia Lagha, Jacques P. Bothma, Emilia Esposito, Samuel Ng, Laura Stefanik, Chiahao Tsui, Jeffrey Johnston, Kai Chen, David S. Gilmour, Julia Zeitlinger, Michael S. Levine

Research output: Contribution to journalArticle

93 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)976
Number of pages1
JournalCell
Volume153
Issue number5
DOIs
StatePublished - May 23 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lagha, M., Bothma, J. P., Esposito, E., Ng, S., Stefanik, L., Tsui, C., Johnston, J., Chen, K., Gilmour, D. S., Zeitlinger, J., & Levine, M. S. (2013). XPaused Pol II coordinates tissue morphogenesis in the drosophila embryo. Cell, 153(5), 976. https://doi.org/10.1016/j.cell.2013.04.045