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Hair is important for thermoregulation, physical protection, sensory activity, seasonal camouflage, and social interactions. Hair is generated in hair follicles (HFs) and, following morphogenesis, HFs undergo cyclic phases of active growth (anagen), regression (catagen), and inactivity (telogen) throughout life. The transcriptional regulation of this process is not well understood. We show that the transcription factor Lhx2 is expressed in cells of the outer root sheath and a subpopulation of matrix cells during both morphogenesis and anagen. As the HFs enter telogen, expression becomes undetectable and reappears prior to initiation of anagen in the secondary hair germ. In contrast to previously published results, we find that Lhx2 is primarily expressed by precursor cells outside of the bulge region where the HF stem cells are located. This developmental, stage- and cell-specific expression suggests that Lhx2 regulates the generation and regeneration of hair. In support of this hypothesis, we show that Lhx2 is required for anagen progression and HF morphogenesis. Moreover, transgenic expression of Lhx2 in postnatal HFs is sufficient to induce anagen. Thus, our results reveal an alternative interpretation of Lhx2 function in HFs compared to previously published results, since Lhx2 is periodically expressed, primarily in precursor cells distinct from those in the bulge region, and is an essential positive regulator of hair formation. Hair is generated in hair follicles, complex mini-organs in the skin that are devoted to this task. All hair follicles are generated during embryonic development. The hair follicles generate a new hair shaft by cycling through stages of regression, rest, and growth continuously throughout life. The length of the growth phase determines the length of the hair. The reason(s) for this complicated regulation of hair growth is not clear, but it has been suggested that it may accommodate seasonal variations in hair growth. In this study we have identified the transcription factor Lhx2 as an important regulator of hair formation. The Lhx2 gene is active during the growth phase of the hair follicle and is turned off during the resting phase. We confirm that Lhx2 is functionally involved in hair formation, since hair follicles where Lhx2 has been inactivated are unable to make hair. Moreover, activation of the Lhx2 gene in hair follicles induced the growth phase and hence hair formation. Thus, Lhx2 is an important regulator of hair growth. Abstract
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Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis.
George Cotsarelis, Tung-Tien Sun, Robert Lavker (1990)
Inconsistent with the view that hair follicle stem cells reside in the matrix area of the hair bulb, we found that label-retaining cells exist exclusively in the bulge area of the mouse hair follicle. The bulge consists of a subpopulation of outer root sheath cells located in the midportion of the follicle at the arrector pili muscle attachment site. Keratinocytes in the bulge area are relatively undifferentiated ultrastructurally. They are normally slow cycling, but can be stimulated to proliferate transiently by TPA. Located in a well-protected and nourished environment, these cells mark the lower end of the "permanent" portion of the follicle. Our findings, plus a reevaluation of the literature, suggest that follicular stem cells reside in the bulge region, instead of the lower bulb. This new view provides insights into hair cycle control and the possible involvement of hair follicle stem cells in skin carcinogenesis.
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The secret life of the hair follicle.
M. Hardy (1992)
The mammalian hair follicle is a treasure waiting to be discovered by more molecular geneticists. How can a tiny cluster of apparently uniform epithelial cells, adjacent to a tiny cluster of uniform mesenchymal cells, give rise to five or six concentric cylinders, each of which is composed of cells of a distinctive type that synthesize their own distinctive set of proteins? There is now evidence that several growth factors, cell adhesion molecules and other molecules play important roles in the regulation of this minute organ.
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Controls of hair follicle cycling.
K Stenn, R Paus (2001)
Nearly 50 years ago, Chase published a review of hair cycling in which he detailed hair growth in the mouse and integrated hair biology with the biology of his day. In this review we have used Chase as our model and tried to put the adult hair follicle growth cycle in perspective. We have tried to sketch the adult hair follicle cycle, as we know it today and what needs to be known. Above all, we hope that this work will serve as an introduction to basic biologists who are looking for a defined biological system that illustrates many of the challenges of modern biology: cell differentiation, epithelial-mesenchymal interactions, stem cell biology, pattern formation, apoptosis, cell and organ growth cycles, and pigmentation. The most important theme in studying the cycling hair follicle is that the follicle is a regenerating system. By traversing the phases of the cycle (growth, regression, resting, shedding, then growth again), the follicle demonstrates the unusual ability to completely regenerate itself. The basis for this regeneration rests in the unique follicular epithelial and mesenchymal components and their interactions. Recently, some of the molecular signals making up these interactions have been defined. They involve gene families also found in other regenerating systems such as fibroblast growth factor, transforming growth factor-beta, Wnt pathway, Sonic hedgehog, neurotrophins, and homeobox. For the immediate future, our challenge is to define the molecular basis for hair follicle growth control, to regenerate a mature hair follicle in vitro from defined populations, and to offer real solutions to our patients' problems.
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Author and article information
Contributors
: Role: Editor
Journal
Journal ID (nlm-ta): PLoS Genet
Journal ID (publisher-id): plos
Journal ID (pmc): plosgen
Title: PLoS Genetics
Publisher: Public Library of Science (San Francisco, USA )
ISSN (Print): 1553-7390
ISSN (Electronic): 1553-7404
Publication date Collection: April 2010
Publication date (Print): April 2010
Publication date (Electronic): 8 April 2010
Volume: 6
Issue: 4
Electronic Location Identifier: e1000904
Affiliations
Author notes
* E-mail: leif.carlsson@ 123456ucmm.umu.se
Article
Publisher ID: 09-PLGE-RA-1868R2
DOI: 10.1371/journal.pgen.1000904
PMC ID: 2851574
PubMed ID: 20386748
SO-VID: b32c4ba1-f933-4e08-8520-efaf112a6ca6
Copyright © Törnqvist et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
History
Date received : 26 October 2009
Date accepted : 9 March 2010
Page count
Pages: 16
Categories
Subject: Research Article
Subject: Cell Biology/Gene Expression
Subject: Dermatology
Subject: Developmental Biology
ScienceOpen disciplines: Genetics
Data availability:
ScienceOpen disciplines: Genetics
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