Shh maintains dermal papilla identity and hair morphogenesis via a Noggin–Shh regulatory loop

Woo, Wei‐Meng; Zhen, Hanson H.; Oro, Anthony E.

doi:10.1101/gad.187401.112

Cited by 147 publications

(134 citation statements)

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“…We have successfully demonstrated dermal specific gene function of a few genes using our hair regeneration assay 1,12 . Based on the GFP marker co-expressed from lentivirus vector expressing shRNA 10 .…”

Section: Discussionmentioning

confidence: 99%

“…This assay allows us to demonstrate gene function in hair follicle formation in as little as three weeks from infecting primary cells with lentivirus to graft collection. Our assay can be extended to address genetic interactions using combination shRNA/cDNA delivery by lentivirus into one cell type 12 , as well as allows examination of signaling between the dermal and epidermal cell types.…”

Section: Discussionmentioning

confidence: 99%

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Rapid Genetic Analysis of Epithelial-Mesenchymal Signaling During Hair Regeneration

Woo

Atwood

Zhen

et al. 2013

JoVE

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Hair follicle morphogenesis, a complex process requiring interaction between epithelia-derived keratinocytes and the underlying mesenchyme, is an attractive model system to study organ development and tissue-specific signaling. Although hair follicle development is genetically tractable, fast and reproducible analysis of factors essential for this process remains a challenge. Here we describe a procedure to generate targeted overexpression or shRNA-mediated knockdown of factors using lentivirus in a tissue-specific manner. Using a modified version of a hair regeneration model 5, 6,11 , we can achieve robust gain-or loss-of-function analysis in primary mouse keratinocytes or dermal cells to facilitate study of epithelial-mesenchymal signaling pathways that lead to hair follicle morphogenesis. We describe how to isolate fresh primary mouse keratinocytes and dermal cells, which contain dermal papilla cells and their precursors, deliver lentivirus containing either shRNA or cDNA to one of the cell populations, and combine the cells to generate fully formed hair follicles on the backs of nude mice. This approach allows analysis of tissue-specific factors required to generate hair follicles within three weeks and provides a fast and convenient companion to existing genetic models. Video LinkThe video component of this article can be found at https://www.jove.com/video/4344/ Protocol 1. Prepare 0 to 2 days Old Newborn Mice for Skin Dissection 1. Euthanize mouse pups using a CO 2 chamber for at least 20 min. Leave pups on ice up to an hour until dissection. P0-P2 mice are highly recommended as cells prepared from older mice have reduced progenitor capacity that results in lower graft yields. Prepare one dish of 70% ethanol (for step 1.3) and three dishes of wash solution (for step 3) when ready to perform skin dissection. Thaw Dispase Solution and leave it at 4 °C. Cervical dislocate pups after CO 2 overexposure to ensure euthanasia. 2. Place euthanized pups in a culture dish on ice and transfer to a sterile flow hood. 3. Wash pups by briefly immersing in 70% ethanol and place onto sterile culture dish. Dissect Mouse Skin1. Cut off each limb and tail at the base of the torso with sterile scissors. 2. Grasp the body firmly between a pair of curved forceps and make an incision along the dorsal skin from head to tail using a scalpel without penetrating the underlying fascia. 3. Carefully peel the skin away from the midline of the mouse. 4. Grasp the exposed mouse firmly with the long side of the curved forceps and insert another pair of curved forceps underneath the skin at the posterior end of the mouse and gently pull skin over hips toward the ventral half of the mouse. 5. Carefully peel skin completely off the mouse in one smooth motion and discard the carcass. Wash Skin and Incubate with Dispase Solution1. Place the skin in the first dish of wash solution with dermis-side down. Spread skin out and agitate with forceps. Leave skin in the first dish of wash solution while dissecting the next skin.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Rapid Genetic Analysis of Epithelial-Mesenchymal Signaling During Hair Regeneration

Woo

Atwood

Zhen

et al. 2013

JoVE

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“…Studies on the HF have emphasized the role of epithelial sonic hedgehog (SHH), downstream of Wnt signaling, in stimulating mesenchymal clustering to form the Nogginexpressing DP (29,30). Because sweat buds display reduced epithelial Wnt signaling and also lack this mesenchymal cluster, we posited that in sweat buds, Shh is silenced, which in turn should be reflected in the failure of foot skin dermis to activate downstream SHHsignaling target genes.…”

Section: All Roads Lead To Suppression Of Shh Signaling In Swg-permismentioning

confidence: 99%

839 Spatiotemporal antagonism in mesenchymal-epithelial Signaling in sweat versus hair fate decision

Polak

Keyes

et al. 2017

Journal of Investigative Dermatology

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The gain of eccrine sweat glands in hairy body skin has empowered humans to run marathons and tolerate temperature extremes. Epithelial-mesenchymal cross-talk is integral to the diverse patterning of skin appendages, but the molecular events underlying their specification remain largely unknown. Using genome-wide analyses and functional studies, we show that sweat glands are specified by mesenchymal-derived bone morphogenetic proteins (BMPs) and fibroblast growth factors that signal to epithelial buds and suppress epithelial-derived sonic hedgehog (SHH) production. Conversely, hair follicles are specified when mesenchymal BMP signaling is blocked, permitting SHH production. Fate determination is confined to a critical developmental window and is regionally specified in mice. In contrast, a shift from hair to gland fates is achieved in humans when a spike in BMP silences SHH during the final embryonic wave(s) of bud morphogenesis.Epithelial appendages-including hair follicles (HFs) and teeth as well as mammary, sweat, and salivary glands-begin to form during embryogenesis when Wnt signaling triggers progenitors within the epithelial sheet to organize spatially into morphologically similar placodes. Whereas most mammals restrict the specification of epidermal appendages regionally, HFs and sweat glands (SwGs) coexist throughout much of the skin of primates. The acquisition of SwGs and their importance in thermoregulation are underscored by humans who suffer from a life-threatening condition when SwGs are eliminated, either from loss in severe burns or from the genetic disorder hypohidrotic ectodermal dysplasia (HED).Patients with HED display mutations in genes encoding proteins such as ectodermal dysplasia antigen (EDA), the EDA receptor (EDAR), and WNT10a, a ligand for Wnt signaling. These findings have illuminated a critical role for these pathways in controlling the development of a number of epidermal appendages, including SwGs and coarse hairs (1, † Corresponding author. fuchslb@rockefeller.edu. * Present address: Calico Life Sciences, South San Francisco, CA 94080, USA.RNAseq data are deposited in the Gene Expression Omnibus under accession number GSE85249 (www.ncbi.nlm.nih.gov/geo).The authors declare no competing financial interests. SUPPLEMENTARY MATERIALS Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript 2). Conversely, an EDAR gain-of-function variant has been expanding among the Southeast Asian population, where excessive SwGs are desirable because of the hot and humid climate of that region (3). In this regard, both Wnt and EDA/EDAR pathways appear to function in promoting placode formation, increasing the density of SwGs and several other appendage types (4).Classical tissue recombination experiments have revealed that mesenchyme plays a critical role in dictating the divergent downstream events that determine appendage selection (5, 6). For example, salivary mesenchyme combined with mammary epithelium generates an epithelial morphology resembling salivary glands (7), and...

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“…It has been described that anagen phase is activated by Wnt (wingless) /β-catenin (Beta-catenin) / LEFT (T-cell factor lymphoid enhancer), Sonic hedgehog (Shh) and the proteyoglican versican [40,41,33]. This molecules have been used as an indicator of hair inductiveness, many of which are also associated with aggregative behaviour.…”

Section: Anatomy and Hair Cyclementioning

confidence: 99%

Androgenetic Alopecia: a Review and Emerging Treatments

Alves¹

2017

CRDOA

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Androgenetic Alopecia (AGA) is the most common noncicatricial alopecia that leads to the progressive miniaturization of the hair follicle. Scalp terminal hairs are converted into vellus hairs, primarily due to two factors: genetic predisposition and hormonal stimulation.The incidence and prevalence of AGA increases with age. The onset of AGA is gradual, and when this pathology progresses, the anagen phase shortens and the telogen phase remains constant. The shedding area varies from patient to patient and is usually most marked at the vertex in men, while women with AGA generally lose hair diffusely over the crown.Topical minoxidil and oral finasteride (5-alpha-reductase type II inhibitor) are the gold-standard therapies for AGA and are currently the only Food and Drug Administration (FDA)-approved drugs for the treatment of AGA.The currently available treatments for AGA are sometimes perceived as having limited effectiveness; therefore, the identification of new therapies for this pathology is of utmost importance.This article aims to review the pathogenesis, diagnosis of AGA and all the new emerging treatments for this entity in order to prevent its progression and improve the results of this pathology.

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Shh maintains dermal papilla identity and hair morphogenesis via a Noggin–Shh regulatory loop

Cited by 147 publications

References 69 publications

Rapid Genetic Analysis of Epithelial-Mesenchymal Signaling During Hair Regeneration

Rapid Genetic Analysis of Epithelial-Mesenchymal Signaling During Hair Regeneration

839 Spatiotemporal antagonism in mesenchymal-epithelial Signaling in sweat versus hair fate decision

Androgenetic Alopecia: a Review and Emerging Treatments

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