Induction of the hair growth phase in postnatal mice by localized transient expression of Sonic hedgehog

Satô, Noboru; Leopold, Philip L.; Crystal, Ronald G.

doi:10.1172/jci7691

Cited by 232 publications

(183 citation statements)

References 53 publications

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“…Treatment of adult mice with an anti-SHH antibody blocks anagen progression and hair regrowth (Wang et al, 2000), indicating that SHH is required for the regenerative function of adult bulge stem cells. Conversely, exogenously administered SHH triggers anagen onset in resting hair follicles and stimulates hair growth (Sato et al, 1999). Consistent with these early reports, recent evidence of Shh expression by the committed progeny of stem cells within the anagen follicle has revealed a feedback mechanism whereby SHH+ progenitor cells signal to their parental quiescent stem cells in the bulge region to trigger stem cell activation and proliferation (Hsu et al, 2014).…”

Section: Hair and Skinsupporting

confidence: 53%

Roles for Hedgehog signaling in adult organ homeostasis and repair

2014

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The hedgehog (HH) pathway is well known for its mitogenic and morphogenic functions during development, and HH signaling continues in discrete populations of cells within many adult mammalian tissues. Growing evidence indicates that HH regulates diverse quiescent stem cell populations, but the exact roles that HH signaling plays in adult organ homeostasis and regeneration remain poorly understood. Here, we review recently identified functions of HH in modulating the behavior of tissue-specific adult stem and progenitor cells during homeostasis, regeneration and disease. We conclude that HH signaling is a key factor in the regulation of adult tissue homeostasis and repair, acting via multiple different routes to regulate distinct cellular outcomes, including maintenance of plasticity, in a context-dependent manner.

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Section: Hair and Skinsupporting

confidence: 53%

Roles for Hedgehog signaling in adult organ homeostasis and repair

2014

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“…Proteins that affect the telogen to anagen transition are candidates for regulation by VDR, as the transition from telogen to anagen is abrogated in VDR-null mice (67). Sonic hedgehog has been shown to stimulate the telogen-to-anagen transition (68) and acts downstream of ␤-catenin. ␤-Catenin is required for fate decisions of stem cells to form follicular rather than epidermal keratinocytes (69), and conditional ablation of ␤-catenin in the skin results in alopecia (69).…”

Section: Resultsmentioning

confidence: 99%

Physical and Functional Interaction between the Vitamin D Receptor and Hairless Corepressor, Two Proteins Required for Hair Cycling

Hsieh

Sisk

Jurutka

et al. 2003

Journal of Biological Chemistry

206

201

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Both the vitamin D receptor (VDR) and hairless (hr) genes play a role in the mammalian hair cycle, as inactivating mutations in either result in total alopecia. VDR is a nuclear receptor that functions as a ligand-activated transcription factor, whereas the hairless gene product (Hr) acts as a corepressor of both the thyroid hormone receptor (TR) and the orphan nuclear receptor, ROR␣. In the present study, we show that VDR-mediated transactivation is strikingly inhibited by coexpression of rat Hr. The repressive effect of Hr is observed on both synthetic and naturally occurring VDR-responsive promoters and also when VDR-mediated transactivation is augmented by overexpression of its heterodimeric partner, retinoid X receptor. Utilizing in vitro pull down methods, we find that Hr binds directly to VDR but insignificantly to nuclear receptors that are not functionally repressed by Hr. Coimmunoprecipitation data demonstrate that Hr and VDR associate in a cellular milieu, suggesting in vivo interaction. The Hr contact site in human VDR is localized to the central portion of the ligand binding domain, a known corepressor docking region in other nuclear receptors separate from the activation function-2 domain. Coimmunoprecipitation and functional studies of Hr deletants reveal that VDR contacts a C-terminal region of Hr that includes motifs required for TR and ROR␣ binding. Finally, in situ hybridization analysis of hr and VDR mRNAs in mouse skin demonstrates colocalization in cells of the hair follicle, consistent with a hypothesized intracellular interaction between these proteins to repress VDR target gene expression, in vivo.Nuclear receptors comprise a family of ligand-activated transcription factors that coordinate physiological and developmental processes by regulating specific changes in gene expression (1, 2). The vitamin D receptor (VDR) 1 mediates signaling by 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) and is a member of the thyroid hormone/retinoic acid receptor subfamily of nuclear receptors that heterodimerize with the retinoid X receptor (RXR) on direct repeat hormone-responsive elements in the promoters of regulated genes (3, 4). Binding of liganded VDR⅐RXR to a vitamin D-responsive element (VDRE) in target genes such as osteocalcin, osteopontin, and vitamin D 24-hydroxylase (CYP24) is accompanied by the recruitment of coactivator proteins (5). VDR coactivators such as steroid receptor coactivator-1 (6), NCoA-62 (7), and vitamin D receptor interacting protein 205 (8) stimulate transcriptional activation by facilitating chromatin remodeling and/or attraction of RNA polymerase II. Although some unliganded nuclear receptors (thyroid hormone and retinoic acid receptors) can mediate repression through association with corepressors such as nuclear receptor corepressor (N-CoR) (9) and silencing mediator for retinoic acid and thyroid hormone receptors (SMRT) (10), evidence suggests that VDR does not associate strongly with these corepressors (9 -12).Targeted gene deletion studies in mice (13, 14) and inactivat...

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“…In addition, Shh is expressed in the mesenchymal part of the hair (Oro and Higgins 2003), suggesting that Shh signaling plays a role in the epithelial-mesenchymal interaction regulating hair cycle. Ectopic administration of Shh or Shh agonists stimulates the proportion of hair in its growing stage (Sato et al 1999;Paladini et al 2005), and administration of Shh inhibitor blocks anagen progression (Wang et al 2000;Silva-Vargas et al 2005), showing that Shh exhibits a role in mediating anagen progression during the hair cycle. Gli2-deficient mice present an arrest in HF development similar to Shhnull mice, which is rescued by overexpression of a constitutively active but not wild-type form of Gli2 in the epidermis , showing that Gli2 expression in the epidermis is essential to mediate Shh signaling during HF morphogenesis.…”

Section: Hf Morphogenesis and Cyclingmentioning

confidence: 99%

Development and Homeostasis of the Skin Epidermis

Sotiropoulou

Blanpain

2012

Cold Spring Harbor Perspectives in Biology

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SUMMARYThe skin epidermis is a stratified epithelium that forms a barrier that protects animals from dehydration, mechanical stress, and infections. The epidermis encompasses different appendages, such as the hair follicle (HF), the sebaceous gland (SG), the sweat gland, and the touch dome, that are essential for thermoregulation, sensing the environment, and influencing social behavior. The epidermis undergoes a constant turnover and distinct stem cells (SCs) are responsible for the homeostasis of the different epidermal compartments. Deregulation of the signaling pathways controlling the balance between renewal and differentiation often leads to cancer formation.

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Induction of the hair growth phase in postnatal mice by localized transient expression of Sonic hedgehog

Cited by 232 publications

References 53 publications

Roles for Hedgehog signaling in adult organ homeostasis and repair

Roles for Hedgehog signaling in adult organ homeostasis and repair

Physical and Functional Interaction between the Vitamin D Receptor and Hairless Corepressor, Two Proteins Required for Hair Cycling

Development and Homeostasis of the Skin Epidermis

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