mTORC1 and mTORC2 regulate skin morphogenesis and epidermal barrier formation

Xiaolei Ding, Wilhelm Bloch, Sandra Iden, Markus A. Rüegg, Michael N. Hall, Maria Leptin, Linda Partridge and Sabine A. Eming ()
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Xiaolei Ding: University of Cologne
Wilhelm Bloch: German Sport University Cologne, Am Sportpark Müngersdorf
Sandra Iden: Center for Molecular Medicine Cologne (CMMC), University of Cologne
Markus A. Rüegg: Biozentrum, University of Basel
Michael N. Hall: Biozentrum, University of Basel
Maria Leptin: Center for Molecular Medicine Cologne (CMMC), University of Cologne
Linda Partridge: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne
Sabine A. Eming: University of Cologne

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract Mammalian target of rapamycin (mTOR), a regulator of growth in many tissues, mediates its activity through two multiprotein complexes, mTORC1 or mTORC2. The role of mTOR signalling in skin morphogenesis and epidermal development is unknown. Here we identify mTOR as an essential regulator in skin morphogenesis by epidermis-specific deletion of Mtor in mice (mTOREKO). mTOREKO mutants are viable, but die shortly after birth due to deficits primarily during the early epidermal differentiation programme and lack of a protective barrier development. Epidermis-specific loss of Raptor, which encodes an essential component of mTORC1, confers the same skin phenotype as seen in mTOREKO mutants. In contrast, newborns with an epidermal deficiency of Rictor, an essential component of mTORC2, survive despite a hypoplastic epidermis and disruption in late stage terminal differentiation. These findings highlight a fundamental role for mTOR in epidermal morphogenesis that is regulated by distinct functions for mTORC1 and mTORC2.

Date: 2016
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DOI: 10.1038/ncomms13226

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