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Patterns of hairless (hr) gene expression in mouse hair follicle morphogenesis and cycling.

ABSTRACT: The hr (hairless) gene encodes a putative transcription factor with restricted expression in the skin and brain. Mutations in the hr locus cause papular atrichia in humans and complete hair loss in mice and other mammals. To further elucidate the role of hr in skin biology, and to identify potential target cells for hr regulation, we studied hr mRNA localization during hair follicle (HF) morphogenesis and cycling in normal C57BL/6J mice. In situ hybridization revealed that hr expression was present in the suprabasal cell layers of the epidermis, whereas the basal and highly differentiated keratinocytes of the granular layer were hr-negative. During the early stages of HF morphogenesis, hr mRNA was detected in the developing hair peg. Later, it became concentrated in the HF infundibulum, in the HF matrix, and in the inner root sheath (IRS), whereas the dermal papilla (DP) and outer root sheath were consistently hr mRNA-negative. During catagen, hr gene expression gradually declined in the regressing IRS, shortly but dramatically increased in the zone of developing club hair, and became up-regulated in the epithelial cells adjacent to the DP. The co-localization of hr mRNA with the site of the morphological defects in mutant skin implicates hr as a key factor in regulating basic cellular processes during catagen, including club hair formation, maintenance of DP-epithelial integrity, IRS disintegration, and keratinocyte apoptosis in the HF matrix.

SUBMITTER: Panteleyev AA

PROVIDER: S-EPMC1850155 | biostudies-literature | 2000 Oct

REPOSITORIES: biostudies-literature

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Patterns of hairless (hr) gene expression in mouse hair follicle morphogenesis and cycling.

Panteleyev A A AA Paus R R Christiano A M AM

The American journal of pathology 20001001 4

The hr (hairless) gene encodes a putative transcription factor with restricted expression in the skin and brain. Mutations in the hr locus cause papular atrichia in humans and complete hair loss in mice and other mammals. To further elucidate the role of hr in skin biology, and to identify potential target cells for hr regulation, we studied hr mRNA localization during hair follicle (HF) morphogenesis and cycling in normal C57BL/6J mice. In situ hybridization revealed that hr expression was pres ...[more]

PMID: 11021810

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Project description:Hair follicles undergo recurrent cycling of controlled growth (anagen), regression (catagen), and relative quiescence (telogen) with a defined periodicity. Taking a genomics approach to study gene expression during synchronized mouse hair follicle cycling, we discovered that, in addition to circadian fluctuation, CLOCK-regulated genes are also modulated in phase with the hair growth cycle. During telogen and early anagen, circadian clock genes are prominently expressed in the secondary hair germ, which contains precursor cells for the growing follicle. Analysis of Clock and Bmal1 mutant mice reveals a delay in anagen progression, and the secondary hair germ cells show decreased levels of phosphorylated Rb and lack mitotic cells, suggesting that circadian clock genes regulate anagen progression via their effect on the cell cycle. Consistent with a block at the G1 phase of the cell cycle, we show a significant upregulation of p21 in Bmal1 mutant skin. While circadian clock mechanisms have been implicated in a variety of diurnal biological processes, our findings indicate that circadian clock genes may be utilized to modulate the progression of non-diurnal cyclic processes. To investigate the molecular control of hair follicle cycling, we profiled mRNA expression in mouse dorsal skin at multiple representative time points in the synchronized second postnatal hair growth cycle and in a depilation-induced hair growth cycle. For profiling of second synchronized and depilation-induced hair growth cycle, the same upper-mid region of dorsal skin was excised from C57BL/6 mice at representative postnatal days (P). The time points for second hair growth cycle are classified into different phases of the hair growth cycle based on established morphological guidelines as follow: early anagen (P23, P25), mid anagen (P27), late anagen (P29, P34), early catagen (P37, P39), mid catagen (P41), and telogen (P44). Depilation-induced hair growth cycle by applying wax/rosin mixture on the dorsal skin of seven-week old mice (all follicles in telogen) was performed on mice. The corresponding phases of the hair growth cycle at number of days following depilation (D) is as follow: early anagen (D3), mid anagen (D5), late anagen (D8, D12), and early catagen (D17). For each time point, multiple biological replicates were profiled, with each mouse dorsal skin separately hybridized to an Affymetrix array.

Dataset Information

Patterns of hairless (hr) gene expression in mouse hair follicle morphogenesis and cycling.

Publications

Patterns of hairless (hr) gene expression in mouse hair follicle morphogenesis and cycling.

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