Mitochondrial function in murine skin epithelium is crucial for hair follicle morphogenesis and epithelial-mesenchymal interactions

Jennifer E. Kloepper, Olivier R. Baris, Karen Reuter, Ken Kobayashi, Daniela Weiland, Silvia Vidali, Desmond J. Tobin, Catherin Niemann, Rudolf J. Wiesner, Ralf Paus

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Here, we studied how epithelial energy metabolism impacts overall skin development by selectively deleting intraepithelial mtDNA in mice by ablating a key maintenance factor (Tfam EKO), which induces loss of function of the electron transport chain (ETC). Quantitative (immuno)histomorphometry demonstrated that Tfam EKO mice showed significantly reduced hair follicle (HF) density and morphogenesis, fewer intrafollicular keratin15+ epithelial progenitor cells, increased apoptosis, and reduced proliferation. Tfam EKO mice also displayed premature entry into (aborted) HF cycling by apoptosis-driven HF regression (catagen). Ultrastructurally, Tfam EKO mice exhibited severe HF dystrophy, pigmentary abnormalities, and telogen-like condensed dermal papillae. Epithelial HF progenitor cell differentiation (Plet1, Lrig1 Lef1, and β-catenin), sebaceous gland development (adipophilin, Scd1, and oil red), and key mediators/markers of epithelial-mesenchymal interactions during skin morphogenesis (NCAM, versican, and alkaline phosphatase) were all severely altered in Tfam EKO mice. Moreover, the number of mast cells, major histocompatibility complex class II+, or CD11b+ immunocytes in the skin mesenchyme was increased, and essentially no subcutis developed. Therefore, in contrast to their epidermal counterparts, pilosebaceous unit stem cells depend on a functional ETC. Most importantly, our findings point toward a frontier in skin biology: the coupling of HF keratinocyte mitochondrial function with the epithelial-mesenchymal interactions that drive overall development of the skin and its appendages.

Original languageEnglish (US)
Pages (from-to)679-689
Number of pages11
JournalJournal of Investigative Dermatology
Volume135
Issue number3
DOIs
StatePublished - Mar 12 2015
Externally publishedYes

Fingerprint

Hair Follicle
Morphogenesis
Skin
Epithelium
Stem Cells
Electron Transport
Versicans
Apoptosis
Neural Cell Adhesion Molecules
Catenins
Sebaceous Glands
Stem cells
Mitochondrial DNA
Mesoderm
Alkaline Phosphatase
Major Histocompatibility Complex
Keratinocytes
Oils
Mast Cells
Energy Metabolism

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Mitochondrial function in murine skin epithelium is crucial for hair follicle morphogenesis and epithelial-mesenchymal interactions. / Kloepper, Jennifer E.; Baris, Olivier R.; Reuter, Karen; Kobayashi, Ken; Weiland, Daniela; Vidali, Silvia; Tobin, Desmond J.; Niemann, Catherin; Wiesner, Rudolf J.; Paus, Ralf.

In: Journal of Investigative Dermatology, Vol. 135, No. 3, 12.03.2015, p. 679-689.

Research output: Contribution to journalArticle

Kloepper, JE, Baris, OR, Reuter, K, Kobayashi, K, Weiland, D, Vidali, S, Tobin, DJ, Niemann, C, Wiesner, RJ & Paus, R 2015, 'Mitochondrial function in murine skin epithelium is crucial for hair follicle morphogenesis and epithelial-mesenchymal interactions', Journal of Investigative Dermatology, vol. 135, no. 3, pp. 679-689. https://doi.org/10.1038/jid.2014.475
Kloepper, Jennifer E. ; Baris, Olivier R. ; Reuter, Karen ; Kobayashi, Ken ; Weiland, Daniela ; Vidali, Silvia ; Tobin, Desmond J. ; Niemann, Catherin ; Wiesner, Rudolf J. ; Paus, Ralf. / Mitochondrial function in murine skin epithelium is crucial for hair follicle morphogenesis and epithelial-mesenchymal interactions. In: Journal of Investigative Dermatology. 2015 ; Vol. 135, No. 3. pp. 679-689.
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AU - Weiland, Daniela

AU - Vidali, Silvia

AU - Tobin, Desmond J.

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