Overexpression of epigen during embryonic development induces reversible, epidermal growth factor receptor-dependent sebaceous gland hyperplasia

Maik Dahlhoff, Daniela Frances, Jennifer E. Kloepper, Ralf Paus, Matthias Schäfer, Catherin Niemann, Marlon R. Schneider

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3086-3095
Number of pages10
JournalMolecular and Cellular Biology
Volume34
Issue number16
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Sebaceous Glands
Epidermal Growth Factor Receptor
Embryonic Development
Hyperplasia
Sebum
Stem Cells
Homeostasis
Epigen
Receptor Protein-Tyrosine Kinases
Transgenes
Keratinocytes
Transgenic Mice
Reference Values
Transcription Factors
Parturition
Ligands
Phenotype
Skin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Overexpression of epigen during embryonic development induces reversible, epidermal growth factor receptor-dependent sebaceous gland hyperplasia. / Dahlhoff, Maik; Frances, Daniela; Kloepper, Jennifer E.; Paus, Ralf; Schäfer, Matthias; Niemann, Catherin; Schneider, Marlon R.

In: Molecular and Cellular Biology, Vol. 34, No. 16, 01.01.2014, p. 3086-3095.

Research output: Contribution to journalArticle

Dahlhoff, Maik ; Frances, Daniela ; Kloepper, Jennifer E. ; Paus, Ralf ; Schäfer, Matthias ; Niemann, Catherin ; Schneider, Marlon R. / Overexpression of epigen during embryonic development induces reversible, epidermal growth factor receptor-dependent sebaceous gland hyperplasia. In: Molecular and Cellular Biology. 2014 ; Vol. 34, No. 16. pp. 3086-3095.
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