The Vitamin D Receptor Is a Wnt Effector That Controls Hair Follicle Differentiation and Specifies Tumor Type in Adult Epidermis

January 2008 in “ PloS one ”

Héctor G. Pálmer, Fernando Anjos‐Afonso, Geert Carmeliet, Hikaru Takeda, Fiona M. Watt

Vitamin D Receptor VDR Wnt effector hair follicle differentiation β-catenin basal cell carcinoma alopecia Wnt signaling

Studysummary This study observed that the vitamin D receptor is crucial for hair follicle formation and altering tumor development in the Wnt signaling pathway, suggesting therapeutic potential for vitamin D analogues in related tumors. Our plain-language summary of this paper — not a Tressless recommendation.

The study demonstrated that the Vitamin D Receptor (VDR) was essential as a Wnt effector for hair follicle differentiation and determining tumor type in adult epidermis. Researchers found that VDR activation, in combination with β-catenin, promoted hair follicle-specific gene expression and prevented undifferentiated basal cell carcinomas. VDR−/− mice developed alopecia at 9 weeks, and the absence of VDR led to impaired hair follicle differentiation and basal cell carcinoma-like tumors. The study suggested that VDR and β-catenin interactions are crucial for hair follicle differentiation and may influence skin tumor phenotypes, with potential therapeutic benefits for tumors with abnormal Wnt signaling.

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This study found that absence of the vitamin D receptor in keratinocytes impairs canonical Wnt signaling and leads to alopecia due to defects in keratinocyte stem cells.

research Defining the Impact of Beta-Catenin/Tcf Transactivation on Epithelial Stem Cells

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research Ligand-Independent Actions of the Vitamin D Receptor Maintain Hair Follicle Homeostasis

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research Transient Activation of Beta-Catenin Signaling in Adult Mouse Epidermis Induces New Hair Follicles, Continuous Activation Maintains Tumors

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This study found that continuous β-catenin signaling in adult mouse epidermis can reprogram hair follicles to form benign tumors, which regress after the signaling is discontinued.

research Manipulation of Stem Cell Proliferation and Lineage Commitment: Visualization of Label-Retaining Cells in Wholemounts of Mouse Epidermis

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This study concluded that label-retaining cells in mouse epidermis differ in their sensitivity to proliferative stimuli, influencing their division and potential transdifferentiation without consistently depleting their population.

research Vitamin D3 Analogs Stimulate Hair Growth in Nude Mice

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In this study, synthetic vitamin D3 analogs stimulated hair growth and formation of normal hair follicles in nude mice, unlike the natural form 1,25 dihydroxyvitamin D3.

research Expression of ΔNLef1 in Mouse Epidermis Results in Differentiation of Hair Follicles into Squamous Epidermal Cysts and Formation of Skin Tumors

297 citations , January 2002 in “Development”

In this study, repressing β-catenin/Lef1 signalling in mouse epidermis led to progressive hair loss, dermal cysts, and spontaneous skin tumors with sebaceous differentiation, indicating altered keratinocyte differentiation and potential tumourigenic processes.

research Metabolic And Cellular Analysis Of Alopecia In Vitamin D Receptor Knockout Mice

137 citations , April 2001 in “Journal of Clinical Investigation”

This study found that alopecia in VDR-null mice persists despite undetectable vitamin D levels, indicating a defect in epithelial-mesenchymal communication due to the absence of ligand-independent receptor function.

research Multiple Roles for Activated LEF/TCF Transcription Complexes During Hair Follicle Development and Differentiation

990 citations , October 1999 in “Development”

This study found that LEF1/TCF3 is necessary but not sufficient for TOPGAL activation in hair follicle development, indicating complex regulation in the skin.

research Cytokeratin 15 Expression in Trichoepitheliomas and a Subset of Basal Cell Carcinomas Suggests They Originate from Hair Follicle Stem Cells

133 citations , March 1999 in “Journal of Cutaneous Pathology”

This study found that keratin 15 expression in trichoepitheliomas and some basal cell carcinomas suggests a link to hair follicle stem cells in the bulge.