Abstract
In mice, rats, and humans, loss of function of Foxn1, a member of the winged helix/forkhead family of transcription factors, leads to macroscopic nudity and an inborn dysgenesis of the thymus. Nude (Foxn1nu/Foxn1nu) mice develop largely normal hair follicles and produce hair shafts. However, presumably because of a lack of certain hair keratins, the hair shafts that are generated twist and coil in the hair follicle infundibulum, which becomes dilated. Since hair shafts fail to penetrate the epidermis, macroscopic nudity results and generates the - grossly misleading - impression that nude mice are hairless. Here, we provide an overview of what is known on the role of Foxn1 in mammalian skin biology, its expression patterns in the hair follicle, its influence on hair follicle function, and onychocyte differentiation. We focus on the mechanisms and signaling pathways by which Foxn1 modulates keratinocyte differentiation in the hair follicle and nail apparatus and summarize the current knowledge on the molecular and functional consequences of a loss of function of the Foxn1 protein in skin. Foxn1 target genes, gene regulation of Foxn, and pharmacological manipulation of the nude phenotype (e.g. by cyclosporine A, KGF, and vitamin D3) are discussed, and important open questions as well as promising research strategies in Foxn1 biology are defined. Taken together, this review aims at delineating why enhanced research efforts in this comparatively neglected field of investigative dermatology promise important new insights into the controls of epithelial differentiation in mammalian skin.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 797-810 |
| Number of pages | 14 |
| Journal | Experimental Dermatology |
| Volume | 14 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2005 |
| Externally published | Yes |
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Keywords
- Foxn1
- Hair
- Keratins
- Nail
- Whn
ASJC Scopus subject areas
- Dermatology
Cite this
Learning from nudity : Lessons from the nude phenotype. / Mecklenburg, Lars; Tychsen, Birte; Paus, Ralf.
In: Experimental Dermatology, Vol. 14, No. 11, 01.11.2005, p. 797-810.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Learning from nudity
T2 - Lessons from the nude phenotype
AU - Mecklenburg, Lars
AU - Tychsen, Birte
AU - Paus, Ralf
PY - 2005/11/1
Y1 - 2005/11/1
N2 - In mice, rats, and humans, loss of function of Foxn1, a member of the winged helix/forkhead family of transcription factors, leads to macroscopic nudity and an inborn dysgenesis of the thymus. Nude (Foxn1nu/Foxn1nu) mice develop largely normal hair follicles and produce hair shafts. However, presumably because of a lack of certain hair keratins, the hair shafts that are generated twist and coil in the hair follicle infundibulum, which becomes dilated. Since hair shafts fail to penetrate the epidermis, macroscopic nudity results and generates the - grossly misleading - impression that nude mice are hairless. Here, we provide an overview of what is known on the role of Foxn1 in mammalian skin biology, its expression patterns in the hair follicle, its influence on hair follicle function, and onychocyte differentiation. We focus on the mechanisms and signaling pathways by which Foxn1 modulates keratinocyte differentiation in the hair follicle and nail apparatus and summarize the current knowledge on the molecular and functional consequences of a loss of function of the Foxn1 protein in skin. Foxn1 target genes, gene regulation of Foxn, and pharmacological manipulation of the nude phenotype (e.g. by cyclosporine A, KGF, and vitamin D3) are discussed, and important open questions as well as promising research strategies in Foxn1 biology are defined. Taken together, this review aims at delineating why enhanced research efforts in this comparatively neglected field of investigative dermatology promise important new insights into the controls of epithelial differentiation in mammalian skin.
AB - In mice, rats, and humans, loss of function of Foxn1, a member of the winged helix/forkhead family of transcription factors, leads to macroscopic nudity and an inborn dysgenesis of the thymus. Nude (Foxn1nu/Foxn1nu) mice develop largely normal hair follicles and produce hair shafts. However, presumably because of a lack of certain hair keratins, the hair shafts that are generated twist and coil in the hair follicle infundibulum, which becomes dilated. Since hair shafts fail to penetrate the epidermis, macroscopic nudity results and generates the - grossly misleading - impression that nude mice are hairless. Here, we provide an overview of what is known on the role of Foxn1 in mammalian skin biology, its expression patterns in the hair follicle, its influence on hair follicle function, and onychocyte differentiation. We focus on the mechanisms and signaling pathways by which Foxn1 modulates keratinocyte differentiation in the hair follicle and nail apparatus and summarize the current knowledge on the molecular and functional consequences of a loss of function of the Foxn1 protein in skin. Foxn1 target genes, gene regulation of Foxn, and pharmacological manipulation of the nude phenotype (e.g. by cyclosporine A, KGF, and vitamin D3) are discussed, and important open questions as well as promising research strategies in Foxn1 biology are defined. Taken together, this review aims at delineating why enhanced research efforts in this comparatively neglected field of investigative dermatology promise important new insights into the controls of epithelial differentiation in mammalian skin.
KW - Foxn1
KW - Hair
KW - Keratins
KW - Nail
KW - Whn
UR - http://www.scopus.com/inward/record.url?scp=27744608594&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27744608594&partnerID=8YFLogxK
U2 - 10.1111/j.1600-0625.2005.00362.x
DO - 10.1111/j.1600-0625.2005.00362.x
M3 - Review article
C2 - 16232301
AN - SCOPUS:27744608594
VL - 14
SP - 797
EP - 810
JO - Experimental Dermatology
JF - Experimental Dermatology
SN - 0906-6705
IS - 11
ER -