mTORC1 and mTORC2 regulate skin morphogenesis and epidermal barrier formation.
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). mTOREKOmutants 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 mTOREKOmutants. 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.
Department of Dermatology, University of Cologne, Kerpenerstr. 62, Cologne 50937, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch-Str. 21, Cologne 50931, Germany.
Xiaolei
X
Ding
Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Am Sportpark Müngersdorf, Cologne 50933, Germany.
Wilhelm
W
Bloch
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch-Str. 21, Cologne 50931, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Str. 26, Cologne 50931, Germany.
Sandra
S
Iden
Biozentrum, University of Basel, Klingelbergstrasse 50/70, Basel CH-4056, Switzerland.
Markus A
MA
Rüegg
Biozentrum, University of Basel, Klingelbergstrasse 50/70, Basel CH-4056, Switzerland.
Michael N
MN
Hall
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch-Str. 21, Cologne 50931, Germany.|Institute for Genetics, University of Cologne, Zülpicherstr. 47a, Cologne 50674, Germany.|European Molecular Biology Laboratory, Meyerhofstr. 1, Heidelberg 69117, Germany.
Maria
0000-0001-7097-348X
M
Leptin
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Str. 26, Cologne 50931, Germany.|Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, Cologne 50931, Germany.|Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, UK.
Linda
L
Partridge
Department of Dermatology, University of Cologne, Kerpenerstr. 62, Cologne 50937, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch-Str. 21, Cologne 50931, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Str. 26, Cologne 50931, Germany.
Sabine A
SA
Eming
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology* / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism*; D000076225:Mechanistic Target of Rapamycin Complex 2 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
C546843:mTOR protein, mouse; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases