Universität zu Köln

Dahlhoff, Maik ORCID: 0000-0001-9189-7631, Frances, Daniela, Kloepper, Jennifer E., Paus, Ralf ORCID: 0000-0002-3492-9358, Schaefer, Matthias, Niemann, Catherin and Schneider, Marlon R. (2014). Overexpression of Epigen during Embryonic Development Induces Reversible, Epidermal Growth Factor Receptor-Dependent Sebaceous Gland Hyperplasia. Mol. Cell. Biol., 34 (16). S. 3086 - 3096. WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-5549

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Abstract

The epidermal growth factor receptor (EGFR) system is a key regulator of epithelial development and homeostasis. Its functions in the sebaceous gland (SG), however, remain poorly characterized. In this study, using a transgenic mouse line with tissue-specific and inducible expression of the EGFR ligand epigen, we showed that increased activation of the EGFR in skin keratinocytes results in enlarged SGs and increased sebum production. The phenotype can be reverted by interrupting transgene expression and is EGFR dependent, as gland size and sebum levels return to normal values after crossing to the EGFR-impaired mouse line Wa5. Intriguingly, however, the SG enlargement appears only if EGFR activation occurs before birth. Importantly, the enlarged sebaceous glands are associated with an increased expression of the transcription factor MYC and of the transmembrane proteins LRIG1, an established negative-feedback regulator of the EGFR/ERBB tyrosine kinase receptors and a stem cell marker. Our findings identify EGFR signaling as a major pathway determining SG activity and suggest a functional relationship between the EGFR/ERBB system and MYC/LRIG1 in the commitment of stem cells toward specific progenitor cell types, with implications for our understanding of their role in tissue development, homeostasis, and disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dahlhoff, Maik UNSPECIFIED orcid.org/0000-0001-9189-7631 UNSPECIFIED Frances, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloepper, Jennifer E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Paus, Ralf UNSPECIFIED orcid.org/0000-0002-3492-9358 UNSPECIFIED Schaefer, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Niemann, Catherin UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Marlon R. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-433041
DOI:	10.1128/MCB.00302-14
Journal or Publication Title:	Mol. Cell. Biol.
Volume:	34
Number:	16
Page Range:	S. 3086 - 3096
Date:	2014
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-5549
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FOLLICLE STEM-CELLS; ERBB NEGATIVE REGULATOR; HAIR FOLLICLE; MOUSE SKIN; COMPREHENSIVE GUIDE; TUMOR-SUPPRESSOR; PROGENITOR CELLS; LRIG1; EXPRESSION; BULGE Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43304