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Temporal regulation of epithelium formation

Stephen E. Von Stetina, Jennifer Liang, Georgios Marnellos, Susan E. Mango
doi: https://doi.org/10.1101/076570
Stephen E. Von Stetina
1Department of Molecular and Cellular Biology, BL3015, 16 Divinity Avenue, Cambridge, MA 02138
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Jennifer Liang
1Department of Molecular and Cellular Biology, BL3015, 16 Divinity Avenue, Cambridge, MA 02138
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Georgios Marnellos
2Informatics and Scientific Applications, Science Division, Faculty of Arts and Sciences, Harvard University,MA 02138, Cambridge USA
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Susan E. Mango
1Department of Molecular and Cellular Biology, BL3015, 16 Divinity Avenue, Cambridge, MA 02138
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Abstract/Summary

To establish the animal body plan, embryos link the external epidermis to the internal digestive tract. In Caenorhabditis elegans, this linkage is achieved by the Arcade Cells, which form an epithelial bridge between the foregut and epidermis, but little is known about how development of these three epithelia is coordinated temporally. The Arcade Cell epithelium is generated after the epidermis and digestive tract epithelia have matured, ensuring that both organs can withstand the mechanical stress of embryo elongation; mis-timing of epithelium formation leads to defects in morphogenesis. Here, we report that temporal regulation of the Arcade Cell epithelium is mediated by the pioneer transcription factor PHA-4/FoxA, the cytoskeletal regulator ZEN-4/MKLP and the polarity protein PAR-6. We find that PHA-4 activates expression of a broad cohort of epithelial genes. However, accumulation of protein is delayed by ZEN-4, acting in concert with its partner CYK-4/MgcRacGAP. Finally, PAR-6 localizes factors within adherens junctions and at the apical surface, leading to Arcade Cell polarity. The results reveal that the timing of a landmark event during embryonic morphogenesis is mediated by the concerted action of four proteins that delay the formation of an epithelial bridge. In addition, we find that FoxA associates with many epithelial genes in mammals, suggesting that regulation of epithelial identity may be a conserved feature of FoxA factors and a contributor to FoxA function in development and cancer.

  • Abbreviations

    ZEN
    Zygotic ENclosure defective
    PAR
    PARtitioning defective
    PHA
    defective PHArynx development
    ERM
    Ezrin/Radixin/Moesin homolog
    DLG
    Disks LarGe
    CYK
    CytoKinesis defective
    Crb
    Crumbs
    Scrib
    Scribble
    LGL
    Lethal Giant Larvae
    FOXA
    Forkhead bOX transcription factor subgroup A
    smFISH
    single molecule Fluorescent In Situ Hybridization
    ChIP-Seq
    Chromatin ImmunoPrecipitation-Sequencing
    TSS
    Transcription Start Site
    MET
    Mesenchymal-to-Epithelial Transition
    EMT
    Epithelial-to-Mesenchymal Transition
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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    Posted September 21, 2016.
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    Temporal regulation of epithelium formation
    Stephen E. Von Stetina, Jennifer Liang, Georgios Marnellos, Susan E. Mango
    bioRxiv 076570; doi: https://doi.org/10.1101/076570
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    Temporal regulation of epithelium formation
    Stephen E. Von Stetina, Jennifer Liang, Georgios Marnellos, Susan E. Mango
    bioRxiv 076570; doi: https://doi.org/10.1101/076570

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