Abstract
Mitotic spindle orientation (SO) is a conserved mechanism that governs cell fate and tissue morphogenesis. In the developing epidermis, a balance between self-renewing symmetric divisions and differentiative asymmetric divisions is necessary for normal development. While the cellular machinery that executes SO is well characterized, the extrinsic cues that guide it are poorly understood. Here, we identified the basal cell adhesion molecule (BCAM), a β1 integrin coreceptor, as a novel regulator of epidermal morphogenesis. In utero RNAi-mediated depletion of Bcam in the mouse embryo did not hinder β1 integrin distribution or cell adhesion and polarity. However, Bcam depletion promoted apoptosis, thinning of the epidermis, and symmetric cell division, and the defects were reversed by concomitant overexpression of the apoptosis inhibitor Xiap. Moreover, in mosaic epidermis, depletion of Bcam or Xiap induced symmetric divisions in neighboring wild-type cells. These results identify apoptosis and epidermal architecture as extrinsic cues that guide SO in the developing epidermis.
Funder
United States - Israel Binational Science Foundation
United States-Israel Binational Science Foundation
Israel Science Foundation
Richard Eimert Research Fund on Solid Tumors of the Faculty of Medicine, Tel Aviv University.
Publisher
Public Library of Science (PLoS)
Subject
General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Neuroscience
Cited by
1 articles.
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