Cutaneous consequences of inhibiting EGF receptor signaling in vivo: Normal hair follicle development, but retarded hair cycle induction and inhibition of adipocyte growth in EgfrWa5 mice

Koji Sugawara, Marlon R. Schneider, Maik Dahlhoff, Jennifer E. Kloepper, Ralf Paus

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: The epidermal growth factor receptor (EGFR) network is essential for proper development and homeostasis of skin and hair. However, detailed dissection of the role of the EGFR in hair follicle development and cycling have been impaired by the early mortality of EGFR knockout mice. Objectives: We have studied in Waved-5 mice carrying an antimorphic EGFR allele (Egfrwa5), whose product acts as a dominant-negative receptor, whether strongly reduced EGFR signaling impacts on the hair and skin phenotype. Methods: Histomorphometry and immunohistochemistry were employed to study hair follicle morphogenesis stages and cycle induction in Waved-5 mice and control littermates during embryonic development and postnatal life. Results: By routine histology and quantitative histomorphometry, no significant abnormalities in the epidermis and in hair follicle morphogenesis were detected, while the initiation of hair follicle cycling was slightly, but significantly retarded. Proliferation and apoptosis of epidermal and hair matrix keratinocytes of Waved-5 mice appeared unaltered. Intriguingly, the thickness of the subcutis and the percentage of proliferating subcutaneous adipocytes were significantly reduced in Waved-5 mice around days P8.5 to P10.5. Although no differences in total body weight gain could be detected, Wa5 mice showed a significant reduction in the percentage of body fat at P8.5. Conclusion: Our results suggest the presence of effective compensatory mechanisms in murine skin in vivo that ensure nearly normal epidermal and hair follicle keratinocyte function despite very low levels of EGFR-mediated signaling. Our unexpected findings of transiently reduced subcutaneous adipose tissue indicate a role for the EGFR in regulating subcutaneous fat.

Original languageEnglish (US)
Pages (from-to)155-161
Number of pages7
JournalJournal of Dermatological Science
Volume57
Issue number3
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

Fingerprint

Hair Follicle
Epidermal Growth Factor Receptor
Adipocytes
Hair
Skin
Growth
Subcutaneous Fat
Morphogenesis
Keratinocytes
Fats
Dissection
Histology
Epidermis
Knockout Mice
Weight Gain
Embryonic Development
Adipose Tissue
Homeostasis
Immunohistochemistry
Alleles

Keywords

  • Adipocytes
  • Apoptosis
  • Catagen
  • EGFR
  • Subcutis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Cutaneous consequences of inhibiting EGF receptor signaling in vivo : Normal hair follicle development, but retarded hair cycle induction and inhibition of adipocyte growth in EgfrWa5 mice. / Sugawara, Koji; Schneider, Marlon R.; Dahlhoff, Maik; Kloepper, Jennifer E.; Paus, Ralf.

In: Journal of Dermatological Science, Vol. 57, No. 3, 01.03.2010, p. 155-161.

Research output: Contribution to journalArticle

@article{89ff08c11ab5434b9d9423672859e4e3,
title = "Cutaneous consequences of inhibiting EGF receptor signaling in vivo: Normal hair follicle development, but retarded hair cycle induction and inhibition of adipocyte growth in EgfrWa5 mice",
abstract = "Background: The epidermal growth factor receptor (EGFR) network is essential for proper development and homeostasis of skin and hair. However, detailed dissection of the role of the EGFR in hair follicle development and cycling have been impaired by the early mortality of EGFR knockout mice. Objectives: We have studied in Waved-5 mice carrying an antimorphic EGFR allele (Egfrwa5), whose product acts as a dominant-negative receptor, whether strongly reduced EGFR signaling impacts on the hair and skin phenotype. Methods: Histomorphometry and immunohistochemistry were employed to study hair follicle morphogenesis stages and cycle induction in Waved-5 mice and control littermates during embryonic development and postnatal life. Results: By routine histology and quantitative histomorphometry, no significant abnormalities in the epidermis and in hair follicle morphogenesis were detected, while the initiation of hair follicle cycling was slightly, but significantly retarded. Proliferation and apoptosis of epidermal and hair matrix keratinocytes of Waved-5 mice appeared unaltered. Intriguingly, the thickness of the subcutis and the percentage of proliferating subcutaneous adipocytes were significantly reduced in Waved-5 mice around days P8.5 to P10.5. Although no differences in total body weight gain could be detected, Wa5 mice showed a significant reduction in the percentage of body fat at P8.5. Conclusion: Our results suggest the presence of effective compensatory mechanisms in murine skin in vivo that ensure nearly normal epidermal and hair follicle keratinocyte function despite very low levels of EGFR-mediated signaling. Our unexpected findings of transiently reduced subcutaneous adipose tissue indicate a role for the EGFR in regulating subcutaneous fat.",
keywords = "Adipocytes, Apoptosis, Catagen, EGFR, Subcutis",
author = "Koji Sugawara and Schneider, {Marlon R.} and Maik Dahlhoff and Kloepper, {Jennifer E.} and Ralf Paus",
year = "2010",
month = "3",
day = "1",
doi = "10.1016/j.jdermsci.2009.12.004",
language = "English (US)",
volume = "57",
pages = "155--161",
journal = "Journal of Dermatological Science",
issn = "0923-1811",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

TY - JOUR

T1 - Cutaneous consequences of inhibiting EGF receptor signaling in vivo

T2 - Normal hair follicle development, but retarded hair cycle induction and inhibition of adipocyte growth in EgfrWa5 mice

AU - Sugawara, Koji

AU - Schneider, Marlon R.

AU - Dahlhoff, Maik

AU - Kloepper, Jennifer E.

AU - Paus, Ralf

PY - 2010/3/1

Y1 - 2010/3/1

N2 - Background: The epidermal growth factor receptor (EGFR) network is essential for proper development and homeostasis of skin and hair. However, detailed dissection of the role of the EGFR in hair follicle development and cycling have been impaired by the early mortality of EGFR knockout mice. Objectives: We have studied in Waved-5 mice carrying an antimorphic EGFR allele (Egfrwa5), whose product acts as a dominant-negative receptor, whether strongly reduced EGFR signaling impacts on the hair and skin phenotype. Methods: Histomorphometry and immunohistochemistry were employed to study hair follicle morphogenesis stages and cycle induction in Waved-5 mice and control littermates during embryonic development and postnatal life. Results: By routine histology and quantitative histomorphometry, no significant abnormalities in the epidermis and in hair follicle morphogenesis were detected, while the initiation of hair follicle cycling was slightly, but significantly retarded. Proliferation and apoptosis of epidermal and hair matrix keratinocytes of Waved-5 mice appeared unaltered. Intriguingly, the thickness of the subcutis and the percentage of proliferating subcutaneous adipocytes were significantly reduced in Waved-5 mice around days P8.5 to P10.5. Although no differences in total body weight gain could be detected, Wa5 mice showed a significant reduction in the percentage of body fat at P8.5. Conclusion: Our results suggest the presence of effective compensatory mechanisms in murine skin in vivo that ensure nearly normal epidermal and hair follicle keratinocyte function despite very low levels of EGFR-mediated signaling. Our unexpected findings of transiently reduced subcutaneous adipose tissue indicate a role for the EGFR in regulating subcutaneous fat.

AB - Background: The epidermal growth factor receptor (EGFR) network is essential for proper development and homeostasis of skin and hair. However, detailed dissection of the role of the EGFR in hair follicle development and cycling have been impaired by the early mortality of EGFR knockout mice. Objectives: We have studied in Waved-5 mice carrying an antimorphic EGFR allele (Egfrwa5), whose product acts as a dominant-negative receptor, whether strongly reduced EGFR signaling impacts on the hair and skin phenotype. Methods: Histomorphometry and immunohistochemistry were employed to study hair follicle morphogenesis stages and cycle induction in Waved-5 mice and control littermates during embryonic development and postnatal life. Results: By routine histology and quantitative histomorphometry, no significant abnormalities in the epidermis and in hair follicle morphogenesis were detected, while the initiation of hair follicle cycling was slightly, but significantly retarded. Proliferation and apoptosis of epidermal and hair matrix keratinocytes of Waved-5 mice appeared unaltered. Intriguingly, the thickness of the subcutis and the percentage of proliferating subcutaneous adipocytes were significantly reduced in Waved-5 mice around days P8.5 to P10.5. Although no differences in total body weight gain could be detected, Wa5 mice showed a significant reduction in the percentage of body fat at P8.5. Conclusion: Our results suggest the presence of effective compensatory mechanisms in murine skin in vivo that ensure nearly normal epidermal and hair follicle keratinocyte function despite very low levels of EGFR-mediated signaling. Our unexpected findings of transiently reduced subcutaneous adipose tissue indicate a role for the EGFR in regulating subcutaneous fat.

KW - Adipocytes

KW - Apoptosis

KW - Catagen

KW - EGFR

KW - Subcutis

UR - http://www.scopus.com/inward/record.url?scp=76349116067&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76349116067&partnerID=8YFLogxK

U2 - 10.1016/j.jdermsci.2009.12.004

DO - 10.1016/j.jdermsci.2009.12.004

M3 - Article

C2 - 20060271

AN - SCOPUS:76349116067

VL - 57

SP - 155

EP - 161

JO - Journal of Dermatological Science

JF - Journal of Dermatological Science

SN - 0923-1811

IS - 3

ER -