Apoptosis and tissue thinning contribute to symmetric cell division in the developing mouse epidermis in a nonautonomous way

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...

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Bibliographic Details
Published in:	PLoS biology Vol. 20; no. 8; p. e3001756
Main Authors:	Soffer, Arad, Mahly, Adnan, Padmanabhan, Krishnanand, Cohen, Jonathan, Adir, Orit, Loushi, Eidan, Fuchs, Yaron, Williams, Scott E, Luxenburg, Chen
Format:	Journal Article
Language:	English
Published:	San Francisco Public Library of Science 15-08-2022 Public Library of Science (PLoS)
Subjects:	Adhesion Apoptosis Biology and Life Sciences Cell adhesion Cell adhesion & migration Cell adhesion molecules Cell division Cell fate Depletion Epidermis Experiments Extracellular matrix Localization Medicine and Health Sciences Morphogenesis Observations Physiological aspects Polarity Proteins Research and Analysis Methods RNA-mediated interference Short Reports Stem cells Thinning XIAP protein United States
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Summary:	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.
Bibliography:	new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors have declared that no competing interests exist.
ISSN:	1545-7885 1544-9173 1545-7885
DOI:	10.1371/journal.pbio.3001756