The role of the hairless (hr) gene in the regulation of hair follicle catagen transformation

Andrei A. Panteleyev, Natalia V. Botchkareva, John P. Sundberg, Angela M. Christiano, Ralf Paus

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Mice that carry a mutation at the hairless (hr) locus develop seemingly normal hair follicles (HF) but shed their hairs completely soon after birth. Histologically, their HFs degenerate into characteristic utriculi and dermal cysts shortly after the entry of the HF into the first regression phase (catagen), during the initiation of HF cycling. Here, we show that at least nine distinct stages of HF disintegration can be distinguished in hr/hr mice. Toward the end of HF morphogenesis (day 15 postpartum) the proximal hair bulb in hr/hr skin undergoes premature and massive apoptosis. This is associated with a dyscoordination of cell proliferation in defined HF compartments, malpositioning of the proximal inner root sheath, striking atrophy of outer root sheath, and failure of trichilemmal keratinization in the developing club hair. Rather than undergoing their normal catagen-associated involution, the hair bulb and central outer root sheath disintegrate into separate cell clusters, thus disrupting all epithelial contact with the dermal papilla. Dermal papilla fibroblasts fail to migrate upward, and break up into clusters of shrunken cells stranded in the reticular dermis as dermal cyst precursors, while the upper HF epithelium transforms into utriculi. Some dermal papilla cells, which normally never undergo apoptosis, also become TUNEL+ in hr/hr skin, and their normally high expression of a key adhesion molecule, neural cell adhesion molecule, declines. Thus, loss of a functional hr gene product (a putative zinc finger transcription factor) initiates a premature, highly dysregulated catagen, which results in the destruction of the normal HF architecture and abrogates the HF's ability to cycle. This provides new insights into the pathobiology of the hr mutation, and suggests that the normal hr gene product is a crucial element of catagen control.

Original languageEnglish (US)
Pages (from-to)159-171
Number of pages13
JournalAmerican Journal of Pathology
Volume155
Issue number1
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

Hair Follicle
Skin
Hair
Genes
Cysts
Apoptosis
Hairless Mouse
Neural Cell Adhesion Molecules
Mutation
Zinc Fingers
In Situ Nick-End Labeling
Ataxia
Dermis
Morphogenesis
Postpartum Period
Atrophy
Transcription Factors
Epithelium
Fibroblasts
Cell Proliferation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

The role of the hairless (hr) gene in the regulation of hair follicle catagen transformation. / Panteleyev, Andrei A.; Botchkareva, Natalia V.; Sundberg, John P.; Christiano, Angela M.; Paus, Ralf.

In: American Journal of Pathology, Vol. 155, No. 1, 01.01.1999, p. 159-171.

Research output: Contribution to journalArticle

Panteleyev, Andrei A. ; Botchkareva, Natalia V. ; Sundberg, John P. ; Christiano, Angela M. ; Paus, Ralf. / The role of the hairless (hr) gene in the regulation of hair follicle catagen transformation. In: American Journal of Pathology. 1999 ; Vol. 155, No. 1. pp. 159-171.
@article{9d9d06122f8049e182ca4052fa849bd5,
title = "The role of the hairless (hr) gene in the regulation of hair follicle catagen transformation",
abstract = "Mice that carry a mutation at the hairless (hr) locus develop seemingly normal hair follicles (HF) but shed their hairs completely soon after birth. Histologically, their HFs degenerate into characteristic utriculi and dermal cysts shortly after the entry of the HF into the first regression phase (catagen), during the initiation of HF cycling. Here, we show that at least nine distinct stages of HF disintegration can be distinguished in hr/hr mice. Toward the end of HF morphogenesis (day 15 postpartum) the proximal hair bulb in hr/hr skin undergoes premature and massive apoptosis. This is associated with a dyscoordination of cell proliferation in defined HF compartments, malpositioning of the proximal inner root sheath, striking atrophy of outer root sheath, and failure of trichilemmal keratinization in the developing club hair. Rather than undergoing their normal catagen-associated involution, the hair bulb and central outer root sheath disintegrate into separate cell clusters, thus disrupting all epithelial contact with the dermal papilla. Dermal papilla fibroblasts fail to migrate upward, and break up into clusters of shrunken cells stranded in the reticular dermis as dermal cyst precursors, while the upper HF epithelium transforms into utriculi. Some dermal papilla cells, which normally never undergo apoptosis, also become TUNEL+ in hr/hr skin, and their normally high expression of a key adhesion molecule, neural cell adhesion molecule, declines. Thus, loss of a functional hr gene product (a putative zinc finger transcription factor) initiates a premature, highly dysregulated catagen, which results in the destruction of the normal HF architecture and abrogates the HF's ability to cycle. This provides new insights into the pathobiology of the hr mutation, and suggests that the normal hr gene product is a crucial element of catagen control.",
author = "Panteleyev, {Andrei A.} and Botchkareva, {Natalia V.} and Sundberg, {John P.} and Christiano, {Angela M.} and Ralf Paus",
year = "1999",
month = "1",
day = "1",
doi = "10.1016/S0002-9440(10)65110-3",
language = "English (US)",
volume = "155",
pages = "159--171",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - The role of the hairless (hr) gene in the regulation of hair follicle catagen transformation

AU - Panteleyev, Andrei A.

AU - Botchkareva, Natalia V.

AU - Sundberg, John P.

AU - Christiano, Angela M.

AU - Paus, Ralf

PY - 1999/1/1

Y1 - 1999/1/1

N2 - Mice that carry a mutation at the hairless (hr) locus develop seemingly normal hair follicles (HF) but shed their hairs completely soon after birth. Histologically, their HFs degenerate into characteristic utriculi and dermal cysts shortly after the entry of the HF into the first regression phase (catagen), during the initiation of HF cycling. Here, we show that at least nine distinct stages of HF disintegration can be distinguished in hr/hr mice. Toward the end of HF morphogenesis (day 15 postpartum) the proximal hair bulb in hr/hr skin undergoes premature and massive apoptosis. This is associated with a dyscoordination of cell proliferation in defined HF compartments, malpositioning of the proximal inner root sheath, striking atrophy of outer root sheath, and failure of trichilemmal keratinization in the developing club hair. Rather than undergoing their normal catagen-associated involution, the hair bulb and central outer root sheath disintegrate into separate cell clusters, thus disrupting all epithelial contact with the dermal papilla. Dermal papilla fibroblasts fail to migrate upward, and break up into clusters of shrunken cells stranded in the reticular dermis as dermal cyst precursors, while the upper HF epithelium transforms into utriculi. Some dermal papilla cells, which normally never undergo apoptosis, also become TUNEL+ in hr/hr skin, and their normally high expression of a key adhesion molecule, neural cell adhesion molecule, declines. Thus, loss of a functional hr gene product (a putative zinc finger transcription factor) initiates a premature, highly dysregulated catagen, which results in the destruction of the normal HF architecture and abrogates the HF's ability to cycle. This provides new insights into the pathobiology of the hr mutation, and suggests that the normal hr gene product is a crucial element of catagen control.

AB - Mice that carry a mutation at the hairless (hr) locus develop seemingly normal hair follicles (HF) but shed their hairs completely soon after birth. Histologically, their HFs degenerate into characteristic utriculi and dermal cysts shortly after the entry of the HF into the first regression phase (catagen), during the initiation of HF cycling. Here, we show that at least nine distinct stages of HF disintegration can be distinguished in hr/hr mice. Toward the end of HF morphogenesis (day 15 postpartum) the proximal hair bulb in hr/hr skin undergoes premature and massive apoptosis. This is associated with a dyscoordination of cell proliferation in defined HF compartments, malpositioning of the proximal inner root sheath, striking atrophy of outer root sheath, and failure of trichilemmal keratinization in the developing club hair. Rather than undergoing their normal catagen-associated involution, the hair bulb and central outer root sheath disintegrate into separate cell clusters, thus disrupting all epithelial contact with the dermal papilla. Dermal papilla fibroblasts fail to migrate upward, and break up into clusters of shrunken cells stranded in the reticular dermis as dermal cyst precursors, while the upper HF epithelium transforms into utriculi. Some dermal papilla cells, which normally never undergo apoptosis, also become TUNEL+ in hr/hr skin, and their normally high expression of a key adhesion molecule, neural cell adhesion molecule, declines. Thus, loss of a functional hr gene product (a putative zinc finger transcription factor) initiates a premature, highly dysregulated catagen, which results in the destruction of the normal HF architecture and abrogates the HF's ability to cycle. This provides new insights into the pathobiology of the hr mutation, and suggests that the normal hr gene product is a crucial element of catagen control.

UR - http://www.scopus.com/inward/record.url?scp=0033017297&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033017297&partnerID=8YFLogxK

U2 - 10.1016/S0002-9440(10)65110-3

DO - 10.1016/S0002-9440(10)65110-3

M3 - Article

C2 - 10393848

AN - SCOPUS:0033017297

VL - 155

SP - 159

EP - 171

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 1

ER -