A role for p75 neurotrophin receptor in the control of hair follicle morphogenesis

Natalia V. Botchkareva, Vladimir A. Botchkarev, Ling Hong Chen, Gerd Lindner, Ralf Paus

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

During hair follicle (HF) morphogenesis, p75 neurotrophin receptor (p75NTR) reportedly is the first growth factor receptor found to be expressed by those fibroblasts that later develop into the dermal papilla [DP) of the HF. However, the functional role of p75NTR in HF morphogenesis is still unknown. Studying HF development in fetal and neonatal C57BL/6 murine back skin, we show that p75NTR-immunoreactivity (IR) is prominently expressed by DP fibroblasts as well as by skin nerves during the early steps of HF development. In contrast, p75NTR-IR disappears from the DP in the fully developed HF and it is expressed only in the epithelial outer root sheath of the HF. Compared to age-matched wild-type animals, p75NTR knockout (-/-) mice show significant acceleration of HF morphogenesis, and DP fibroblasts of p75NTR knockout mice show reduced proliferative activity in situ, indicating alterations in their transition from proliferation to differentiation. Although no significant differences in the expression of adhesion molecules (NCAM), selected morphogens (TGFβ-2, HGF/SF, FGF-2, KGF), or their receptors (TGFβR-II, m-met, FGFR-1) were seen between DP of p75NTR knockout and wild- type mice, p75NTR mutants showed a prominent upregulation of FGFR-2, a high- affinity receptor for KGF, in both follicular DP and epithelium. Furthermore, the administration of anti-KGF neutralizing antibody significantly inhibited acceleration of HF morphogenesis in p75NTR knockout mice in vivo. These observations suggest that p75NTR plays an important role during HF morphogenesis, functioning as a receptor that negatively controls HF development, most likely via alterations in DP fibroblast proliferation/differentiation and via downregulation of KGF/FGFR-2 signaling in the HF.

Original languageEnglish (US)
Pages (from-to)135-153
Number of pages19
JournalDevelopmental Biology
Volume216
Issue number1
DOIs
StatePublished - Dec 1 1999
Externally publishedYes

Fingerprint

Nerve Growth Factor Receptor
Hair Follicle
Morphogenesis
Skin
Knockout Mice
Fibroblasts
Neural Cell Adhesion Molecules
Wild Animals
Growth Factor Receptors
Fibroblast Growth Factor 2
Fetal Development
Neutralizing Antibodies
Up-Regulation
Down-Regulation
Epithelium

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

A role for p75 neurotrophin receptor in the control of hair follicle morphogenesis. / Botchkareva, Natalia V.; Botchkarev, Vladimir A.; Chen, Ling Hong; Lindner, Gerd; Paus, Ralf.

In: Developmental Biology, Vol. 216, No. 1, 01.12.1999, p. 135-153.

Research output: Contribution to journalArticle

Botchkareva, Natalia V. ; Botchkarev, Vladimir A. ; Chen, Ling Hong ; Lindner, Gerd ; Paus, Ralf. / A role for p75 neurotrophin receptor in the control of hair follicle morphogenesis. In: Developmental Biology. 1999 ; Vol. 216, No. 1. pp. 135-153.
@article{7bb986b6094c4632a228d062af0b1ce3,
title = "A role for p75 neurotrophin receptor in the control of hair follicle morphogenesis",
abstract = "During hair follicle (HF) morphogenesis, p75 neurotrophin receptor (p75NTR) reportedly is the first growth factor receptor found to be expressed by those fibroblasts that later develop into the dermal papilla [DP) of the HF. However, the functional role of p75NTR in HF morphogenesis is still unknown. Studying HF development in fetal and neonatal C57BL/6 murine back skin, we show that p75NTR-immunoreactivity (IR) is prominently expressed by DP fibroblasts as well as by skin nerves during the early steps of HF development. In contrast, p75NTR-IR disappears from the DP in the fully developed HF and it is expressed only in the epithelial outer root sheath of the HF. Compared to age-matched wild-type animals, p75NTR knockout (-/-) mice show significant acceleration of HF morphogenesis, and DP fibroblasts of p75NTR knockout mice show reduced proliferative activity in situ, indicating alterations in their transition from proliferation to differentiation. Although no significant differences in the expression of adhesion molecules (NCAM), selected morphogens (TGFβ-2, HGF/SF, FGF-2, KGF), or their receptors (TGFβR-II, m-met, FGFR-1) were seen between DP of p75NTR knockout and wild- type mice, p75NTR mutants showed a prominent upregulation of FGFR-2, a high- affinity receptor for KGF, in both follicular DP and epithelium. Furthermore, the administration of anti-KGF neutralizing antibody significantly inhibited acceleration of HF morphogenesis in p75NTR knockout mice in vivo. These observations suggest that p75NTR plays an important role during HF morphogenesis, functioning as a receptor that negatively controls HF development, most likely via alterations in DP fibroblast proliferation/differentiation and via downregulation of KGF/FGFR-2 signaling in the HF.",
author = "Botchkareva, {Natalia V.} and Botchkarev, {Vladimir A.} and Chen, {Ling Hong} and Gerd Lindner and Ralf Paus",
year = "1999",
month = "12",
day = "1",
doi = "10.1006/dbio.1999.9464",
language = "English (US)",
volume = "216",
pages = "135--153",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - A role for p75 neurotrophin receptor in the control of hair follicle morphogenesis

AU - Botchkareva, Natalia V.

AU - Botchkarev, Vladimir A.

AU - Chen, Ling Hong

AU - Lindner, Gerd

AU - Paus, Ralf

PY - 1999/12/1

Y1 - 1999/12/1

N2 - During hair follicle (HF) morphogenesis, p75 neurotrophin receptor (p75NTR) reportedly is the first growth factor receptor found to be expressed by those fibroblasts that later develop into the dermal papilla [DP) of the HF. However, the functional role of p75NTR in HF morphogenesis is still unknown. Studying HF development in fetal and neonatal C57BL/6 murine back skin, we show that p75NTR-immunoreactivity (IR) is prominently expressed by DP fibroblasts as well as by skin nerves during the early steps of HF development. In contrast, p75NTR-IR disappears from the DP in the fully developed HF and it is expressed only in the epithelial outer root sheath of the HF. Compared to age-matched wild-type animals, p75NTR knockout (-/-) mice show significant acceleration of HF morphogenesis, and DP fibroblasts of p75NTR knockout mice show reduced proliferative activity in situ, indicating alterations in their transition from proliferation to differentiation. Although no significant differences in the expression of adhesion molecules (NCAM), selected morphogens (TGFβ-2, HGF/SF, FGF-2, KGF), or their receptors (TGFβR-II, m-met, FGFR-1) were seen between DP of p75NTR knockout and wild- type mice, p75NTR mutants showed a prominent upregulation of FGFR-2, a high- affinity receptor for KGF, in both follicular DP and epithelium. Furthermore, the administration of anti-KGF neutralizing antibody significantly inhibited acceleration of HF morphogenesis in p75NTR knockout mice in vivo. These observations suggest that p75NTR plays an important role during HF morphogenesis, functioning as a receptor that negatively controls HF development, most likely via alterations in DP fibroblast proliferation/differentiation and via downregulation of KGF/FGFR-2 signaling in the HF.

AB - During hair follicle (HF) morphogenesis, p75 neurotrophin receptor (p75NTR) reportedly is the first growth factor receptor found to be expressed by those fibroblasts that later develop into the dermal papilla [DP) of the HF. However, the functional role of p75NTR in HF morphogenesis is still unknown. Studying HF development in fetal and neonatal C57BL/6 murine back skin, we show that p75NTR-immunoreactivity (IR) is prominently expressed by DP fibroblasts as well as by skin nerves during the early steps of HF development. In contrast, p75NTR-IR disappears from the DP in the fully developed HF and it is expressed only in the epithelial outer root sheath of the HF. Compared to age-matched wild-type animals, p75NTR knockout (-/-) mice show significant acceleration of HF morphogenesis, and DP fibroblasts of p75NTR knockout mice show reduced proliferative activity in situ, indicating alterations in their transition from proliferation to differentiation. Although no significant differences in the expression of adhesion molecules (NCAM), selected morphogens (TGFβ-2, HGF/SF, FGF-2, KGF), or their receptors (TGFβR-II, m-met, FGFR-1) were seen between DP of p75NTR knockout and wild- type mice, p75NTR mutants showed a prominent upregulation of FGFR-2, a high- affinity receptor for KGF, in both follicular DP and epithelium. Furthermore, the administration of anti-KGF neutralizing antibody significantly inhibited acceleration of HF morphogenesis in p75NTR knockout mice in vivo. These observations suggest that p75NTR plays an important role during HF morphogenesis, functioning as a receptor that negatively controls HF development, most likely via alterations in DP fibroblast proliferation/differentiation and via downregulation of KGF/FGFR-2 signaling in the HF.

UR - http://www.scopus.com/inward/record.url?scp=0032736742&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032736742&partnerID=8YFLogxK

U2 - 10.1006/dbio.1999.9464

DO - 10.1006/dbio.1999.9464

M3 - Article

C2 - 10588868

AN - SCOPUS:0032736742

VL - 216

SP - 135

EP - 153

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 1

ER -