Semaphorin-plexin signaling controls mitotic spindle orientation during epithelial morphogenesis and repair

• Published in: Developmental cell 2015-05, Vol.33 (3), p.299-313
• Main Authors: Xia, Jingjing, Swiercz, Jakub M., Bañón-Rodríguez, Inmaculada, Matković, Ivana, Frederico, Giuseppina, Sun, Tianliang, Franz, Timo, Brakebusch, Cord H., Kumanogoh, Atsushi, Friedel, Roland H., Martín-Belmonte, Fernando, Gröne, Hermann-Josef, Offermanns, Stefan, Worzfeld, Thomas
• Format: Article
• Language: English
• Subjects: Animals; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Communication - genetics; Cell Division - physiology; Cell Polarity - physiology; Epithelial Cells - cytology; Epithelium - metabolism; GTPase-Activating Proteins - metabolism; Kidney - embryology; Kidney - metabolism; Male; Mice; Morphogenesis - physiology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Semaphorins - genetics; Semaphorins - metabolism; Signal Transduction - physiology; Spindle Apparatus - genetics; Spindle Apparatus - metabolism; Wound Healing - genetics
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2015.02.001

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. -Epithelial cell-cell communication via plexins orients the mitotic spindle-Loss of Plexin-B1 and Plexin-B2 results in defective kidney morphogenesis-Semaphorin-Plexin-B2 signaling is essential for kidney repair-Plexin-B2 signals through its GAP domain and Cdc42 to orient the mitotic spindle