Hedgehog Signaling, Keratin 6 Induction, And Sebaceous Gland Morphogenesis

August 2008 in “ American Journal Of Pathology ”

Li-Hong Gu, Pierre A. Coulombe

Hedgehog signaling keratin 6a sebaceous gland morphogenesis Wnt signaling hair follicle regulation pachyonychia congenita

Studysummary This study found that K6a expression in mouse sebaceous gland ducts correlates with Hedgehog signaling, suggesting a role in duct fate. Our plain-language summary of this paper — not a Tressless recommendation.

The study investigated the role of Hedgehog (Hh) signaling in sebaceous gland (SG) morphogenesis and its relationship with keratin 6a (K6a) expression using a mouse model. It found that Hh signaling was crucial for SG development, with increased Hh signaling leading to abnormal SGs with elongated ducts and increased K6a expression. This suggested that K6a could serve as a marker for ductal tissue in SGs. The research highlighted the potential regulatory role of Hh signaling in K6a expression and its implications for understanding appendageal defects in conditions like pachyonychia congenita. The study also noted the involvement of other pathways, such as Wnt signaling, in hair follicle and SG regulation, contributing to the understanding of skin and hair-related conditions.

View this study on ajp.amjpathol.org →

Discuss this study in the Community →

Research cited in this study

26 / 26 results

research More Than One Way to Skin

218 citations , April 2008 in “Genes & Development”

This research discusses how epithelial stem cells in the skin maintain normal homeostasis, contribute to wound repair, and highlights the importance of these processes, as defects can lead to skin diseases including cancers, but provides no new experimental results.

research Keratin Expression Provides Novel Insight Into the Morphogenesis and Function of the Companion Layer in Hair Follicles

38 citations , December 2006 in “Journal of Investigative Dermatology”

Keratin patterns in hair follicles help understand hair growth and potential hair and nail disorders.

research Keratin 17 Modulates Hair Follicle Cycling in a TNFα-Dependent Fashion

169 citations , May 2006 in “Genes & Development”

This study found that keratin 17 and TNFα play interdependent roles in regulating hair follicle cycling, with TNFα required for the anagen–catagen transition and its ablation partially rescuing hair cycling defects in K17-null mice.

research Stem Cells in the Hair Follicle Bulge Contribute to Wound Repair but Not to Homeostasis of the Epidermis

1279 citations , November 2005 in “Nature Medicine”

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 Modulation of Hair Growth with Small Molecule Agonists of the Hedgehog Signaling Pathway

113 citations , September 2005 in “Journal of Investigative Dermatology”

This study found that a topical hedgehog agonist can stimulate hair growth by promoting the transition from the resting to growth phase of the hair cycle in adult mouse skin.

research Exploiting the Keratin 17 Gene Promoter to Visualize Live Cells in Epithelial Appendages of Mice

58 citations , July 2005 in “Molecular and Cellular Biology”

This study showed that a 2-kilobase upstream region of the mouse keratin 17 gene enables targeted GFP expression in major epithelial appendages of transgenic mice, indicating sonic hedgehog's involvement in its regulation.

research FOXE1, A New Transcriptional Target Of GLI2, Is Expressed In Human Epidermis And Basal Cell Carcinoma

92 citations , May 2004 in “Journal of Investigative Dermatology”

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

335 citations , March 2004 in “Development”

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 Type II Epithelial Keratin 6hf (K6hf) Is Expressed in the Companion Layer, Matrix, and Medulla in Anagen-Stage Hair Follicles

60 citations , December 2003 in “Journal of Investigative Dermatology”

This study found that keratin 6hf, a type II keratin, is expressed in specific regions of mouse and human hair and suggests potential interactions with keratin 17, impacting hair development and associated disorders.

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

421 citations , September 2003 in “Development”

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 Keratin 16 Expression Defines a Subset of Epithelial Cells During Skin Morphogenesis and the Hair Cycle

87 citations , November 2002 in “Journal of Investigative Dermatology”

research Keratin 17 Null Mice Exhibit Age- And Strain-Dependent Alopecia

122 citations , June 2002 in “Genes & Development”

This study found that K17 is crucial for the structural integrity and survival of hair-producing cells, with K17 null mice developing alopecia due to hair fragility and follicular alterations.

research Discovery of a Novel Murine Keratin 6 (K6) Isoform Explains the Absence of Hair and Nail Defects in Mice Deficient for K6a and K6b

101 citations , August 2001 in “The Journal of Cell Biology”

This study found that while most mice lacking MK6a and MK6b genes died from tongue epithelium disintegration, about 25% survived and showed no hair or nail defects due to a newly discovered MK6hf gene.

research Deregulated Expression of c-Myc Depletes Epidermal Stem Cells

315 citations , June 2001 in “Nature Genetics”

research Delayed Wound Healing in Keratin 6a Knockout Mice

149 citations , July 2000 in “Molecular and Cellular Biology”

This study found that MK6a-deficient mice showed delayed reepithelialization after superficial wounding but not after full-thickness skin wounds, suggesting MK6a plays a role in activating follicular keratinocytes post-wounding.

research Keratin 17 Expression in the Hard Epithelial Context of the Hair and Nail, and Its Relevance for the Pachyonychia Congenita Phenotype

88 citations , June 2000 in “Journal of Investigative Dermatology”

Keratin 17 is important for hair and nail structure and affects pachyonychia congenita symptoms.

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 Cytokeratin Expression in Trichoblastic Fibroma, Trichoepithelioma, and Basal Cell Carcinoma

87 citations , January 1999 in “British Journal of Dermatology”

This study found that trichoblastic fibroma and basal cell carcinoma cannot be differentiated by cytokeratin expression patterns, while trichoepithelioma lacks CK7 expression, distinguishing it from the other two neoplasms.

research Onset of Keratin 17 Expression Coincides with the Definition of Major Epithelial Lineages During Skin Development

318 citations , October 1998 in “The Journal of Cell Biology”

This study found that ectopic expression of the lymphoid-enhancer factor can induce K17 protein in the skin, suggesting a link between skin development and wound repair processes in mice.

research Keratin 17 Mutations Cause Either Steatocystoma Multiplex or Pachyonychia Congenita Type 2

175 citations , September 1998 in “British Journal of Dermatology”

This study found that mutations in the K17 gene underlie both pachyonychia congenita type 2 and steatocystoma multiplex phenotypes, regardless of the specific mutation involved.

research Towards Defining the Pathogenesis of the Hairless Phenotype

86 citations , June 1998 in “Journal of Investigative Dermatology”

This study found that mutations in the hairless gene in mice disrupt hair follicle integrity during catagen, leading to baldness due to disintegrating epithelial structures and loss of normal dermal papilla.

research Defining a Region of the Human Keratin 6a Gene That Confers Inducible Expression in Stratified Epithelia of Transgenic Mice

44 citations , May 1997 in “Journal of Biological Chemistry”

This study found that regulatory sequences crucial for inducing K6a expression in response to epidermal injury are located in specific upstream regions of the K6a gene in transgenic mice.

research Mutation of a Type II Keratin Gene (K6a) in Pachyonychia Congenita

232 citations , July 1995 in “Nature Genetics”

research Keratin Expression in Basal Cell Carcinomas

128 citations , February 1992 in “British Journal of Dermatology”

The researchers reported that basal cell carcinoma tumor cells strongly express keratins typical of basal keratinocytes and some hair follicle components but lack differentiation markers, suggesting a follicular or pluripotent stem cell origin.