Lymphoid Enhancer-Binding Factor-1 Interacts with the DNA-Binding Domain of the Vitamin D Receptor

April 2011 in “ Journal of Biological Chemistry ”

Hilary F. Luderer, Francesca Gori, Marie B. Demay

Vitamin D Receptor Lymphoid Enhancer-binding Factor-1 keratinocytes Wnt signaling hair follicle regeneration alopecia totalis Hedgehog signaling pathways VDR LEF1 skin cells hair loss hair growth

Studysummary This study discovered a novel interaction between the vitamin D receptor and LEF1, essential for normal Wnt signaling in keratinocytes, which is crucial for regular hair cycling.

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The document from May 1, 2011, details a study on the interaction between the Vitamin D Receptor (VDR) and Lymphoid Enhancer-binding Factor-1 (LEF1) in keratinocytes. The study discovered that VDR interacts with the DNA-binding domain of LEF1 independently of β-catenin, which is essential for normal Wnt signaling, a pathway important for hair follicle regeneration. Mutations in the VDR that disrupt this interaction impair the VDR's ability to enhance Wnt signaling, which could have implications for hair loss conditions like alopecia totalis. The research provides insights into the molecular mechanisms of VDR in skin and hair follicle biology, particularly its role in the regulation of Wnt and Hedgehog signaling pathways. The study was based on cellular and molecular experiments and did not involve human subjects.

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Research cited in this study

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research Disruption of the Hedgehog Signaling Pathway Contributes to Hair Follicle Cycling Deficiency in VDR Knockout Mice

53 citations , May 2010 in “Journal of Cellular Physiology”

This study found that mice lacking the Vitamin D receptor showed disrupted hair follicle cycling, which was partially restored with hedgehog signaling pathway activation, suggesting a role for this pathway in follicle regulation independent of vitamin D.

research Embryonic Hair Follicle Fate Change by Augmented Beta-Catenin Through Shh and Bmp Signaling

54 citations , January 2009 in “Development”

This study concluded that Wnt/β-catenin signaling, through Shh and Bmp pathways, is crucial for determining hair follicle fate in embryonic epidermal development.

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

127 citations , January 2008 in “PloS one”

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.

research Vitamin D Receptor Is Essential For Normal Keratinocyte Stem Cell Function

143 citations , May 2007 in “Proceedings of the National Academy of Sciences”

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 Hairless and Wnt Signaling: Allies in Epithelial Stem Cell Differentiation

74 citations , September 2006 in “Cell Cycle”

This review examines the role of Hairless, a nuclear receptor corepressor, in regulating Wnt signaling during hair cycling and reports no new clinical results.

research Hairless Triggers Reactivation of Hair Growth by Promoting Wnt Signaling

137 citations , September 2005 in “Proceedings of the National Academy of Sciences of the United States of America”

In this study, researchers found that transgenic expression of the Hairless gene in keratinocytes can restore hair follicle regeneration in Hr-deficient mice by repressing Wise, a modulator of Wnt signaling.

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

144 citations , December 2004 in “Molecular Endocrinology”

This study found that the effects of the vitamin D receptor on hair follicle cycling in mice are independent of its ability to bind a hormone, with specific domain mutations influencing hair regrowth outcomes.

research Physical And Functional Interaction Between The Vitamin D Receptor And Hairless Corepressor, Two Proteins Required For Hair Cycling

215 citations , September 2003 in “Journal of Biological Chemistry”

This study found that the hairless gene product (Hr) suppresses VDR-mediated gene activation by directly interacting with the vitamin D receptor, potentially affecting hair follicle function.

research Deletion of DNA Binding Domain of the Vitamin D Receptor Abrogates Genomic and Nongenomic Functions of Vitamin D

277 citations , July 2002 in “Molecular Endocrinology”

In this study, homozygous VDR null mutant mice exhibited nonfunctional vitamin D receptors, leading to growth abnormalities and revealing the limited physiological importance of vitamin D pathways outside the classical receptor.

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 Tcf3 and Lef1 Regulate Lineage Differentiation of Multipotent Stem Cells in Skin

555 citations , July 2001 in “Genes & Development”

This study found that Tcf3 and Lef1 differently regulate cell differentiation in multipotent skin stem cells, with Tcf3 promoting follicle-like features and Lef1, when modified, promoting sebocyte differentiation.

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 Conditional Disruption of Hedgehog Signaling Pathway Defines Its Critical Role in Hair Development and Regeneration

194 citations , May 2000 in “Journal of Investigative Dermatology”

This study demonstrated that blocking the Sonic hedgehog signaling pathway in mice led to reversible inhibition of body coat hair morphogenesis, while whisker development was unaffected.

research Induction of the Hair Growth Phase in Postnatal Mice by Localized Transient Expression of Sonic Hedgehog

231 citations , October 1999 in “Journal of Clinical Investigation”

This study found that administering an adenovirus vector to increase Sonic hedgehog gene expression in mouse skin accelerated the transition of hair follicles into the growth phase, promoting hair growth.

research Normalization of Mineral Ion Homeostasis by Dietary Means Prevents Hyperparathyroidism, Rickets, and Osteomalacia, But Not Alopecia in Vitamin D Receptor-Ablated Mice

519 citations , October 1998 in “Endocrinology”

The study found that normalizing mineral ion levels in vitamin D receptor-ablated mice prevented hyperparathyroidism and bone disorders but did not address hair loss, indicating the VDR's role in hair growth.

research Alopecia Universalis Associated With a Mutation in the Human Hairless Gene

412 citations , January 1998 in “Science”

This study identified a missense mutation in the human hairless gene associated with a rare form of recessively inherited alopecia universalis, pinpointed on chromosome 8p12.