Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair

Jingjing Xia, Jakub M. Swiercz, Inmaculada Bañón-Rodríguez, Ivana Matković, Giuseppina Federico, Tianliang Sun, Timo Franz, Cord H. Brakebusch, Atsushi Kumanogoh, Roland H. Friedel, Fernando Martín-Belmonte, Hermann Josef Gröne, Stefan Offermanns, Thomas Worzfeld

    Research output: Contribution to journalArticle

    22 Scopus citations

    Abstract

    Morphogenesis, homeostasis, and regeneration of epithelial tissues rely on the accurate orientation of cell divisions, which is specified by the mitotic spindle axis. To remain in the epithelial plane, symmetrically dividing epithelial cells align their mitotic spindle axis with the plane. Here, we show that this alignment depends on epithelial cell-cell communication via semaphorin-plexin signaling. During kidney morphogenesis and repair, renal tubular epithelial cells lacking the transmembrane receptor Plexin-B2 or its semaphorin ligands fail to correctly orient the mitotic spindle, leading to severe defects in epithelial architecture and function. Analyses of a series of transgenic and knockout mice indicate that Plexin-B2 controls the cell division axis by signaling through its GTPase-activating protein (GAP) domain and Cdc42. Our data uncover semaphorin-plexin signaling as a central regulatory mechanism of mitotic spindle orientation necessary for the alignment of epithelial cell divisions with the epithelial plane.

    Original languageEnglish (US)
    Pages (from-to)299-313
    Number of pages15
    JournalDevelopmental cell
    Volume33
    Issue number3
    DOIs
    StatePublished - May 4 2015

    ASJC Scopus subject areas

    • Molecular Biology
    • Biochemistry, Genetics and Molecular Biology(all)
    • Developmental Biology
    • Cell Biology

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  • Cite this

    Xia, J., Swiercz, J. M., Bañón-Rodríguez, I., Matković, I., Federico, G., Sun, T., Franz, T., Brakebusch, C. H., Kumanogoh, A., Friedel, R. H., Martín-Belmonte, F., Gröne, H. J., Offermanns, S., & Worzfeld, T. (2015). Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair. Developmental cell, 33(3), 299-313. https://doi.org/10.1016/j.devcel.2015.02.001