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Dev Cell. 2015 May 4;33(3):299-313. doi: 10.1016/j.devcel.2015.02.001. Epub 2015 Apr 16.

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

Author information

1
Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
2
Centro de Biología Molecular Severo Ochoa, 28049 Madrid, Spain.
3
Institute of Pharmacology, Biochemical-Pharmacological Center (BPC), University of Marburg, 35043 Marburg, Germany.
4
Department of Cellular and Molecular Pathology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
5
Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark.
6
Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University, Osaka 565-0871, Japan.
7
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
8
Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany; Medical Faculty, University of Frankfurt, 60590 Frankfurt, Germany.
9
Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany; Institute of Pharmacology, Biochemical-Pharmacological Center (BPC), University of Marburg, 35043 Marburg, Germany. Electronic address: thomas.worzfeld@staff.uni-marburg.de.

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.

PMID:
25892012
DOI:
10.1016/j.devcel.2015.02.001
[Indexed for MEDLINE]
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