2016
DOI: 10.1038/ncomms10537
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Epidermal β-catenin activation remodels the dermis via paracrine signalling to distinct fibroblast lineages

Abstract: Sustained epidermal Wnt/β-catenin signalling expands the stem cell compartment and induces ectopic hair follicles (EFs). This is accompanied by extensive fibroblast proliferation and extracellular matrix (ECM) remodelling in the underlying dermis. Here we show that epidermal Hedgehog (Hh) and Transforming growth factor-beta (TGF-β) signalling mediate the dermal changes. Pharmacological inhibition or genetic deletion of these pathways prevents β-catenin-induced dermal reprogramming and EF formation. Epidermal S… Show more

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Cited by 105 publications
(148 citation statements)
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References 52 publications
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“…Epidermal overexpression of the Wnt downstream effector β-catenin in all basal epidermal keratinocytes via the keratin 14 (K14) promoter leads to de novo hair follicle morphogenesis in adult skin; this is accompanied by extensive remodeling of the dermis ECM (105). These effects are mediated by both TGF-β and Hedgehog signaling (106) and influence the lower and upper dermal fibroblast lineages, respectively. Pharmacological deletion or genetic ablation of these pathways prevents the response to epidermal Wnt/β-catenin overexpression (106).…”
Section: Extrinsic Factors Governing Fibroblast Cellular Identitymentioning
confidence: 99%
See 1 more Smart Citation
“…Epidermal overexpression of the Wnt downstream effector β-catenin in all basal epidermal keratinocytes via the keratin 14 (K14) promoter leads to de novo hair follicle morphogenesis in adult skin; this is accompanied by extensive remodeling of the dermis ECM (105). These effects are mediated by both TGF-β and Hedgehog signaling (106) and influence the lower and upper dermal fibroblast lineages, respectively. Pharmacological deletion or genetic ablation of these pathways prevents the response to epidermal Wnt/β-catenin overexpression (106).…”
Section: Extrinsic Factors Governing Fibroblast Cellular Identitymentioning
confidence: 99%
“…These effects are mediated by both TGF-β and Hedgehog signaling (106) and influence the lower and upper dermal fibroblast lineages, respectively. Pharmacological deletion or genetic ablation of these pathways prevents the response to epidermal Wnt/β-catenin overexpression (106).…”
Section: Extrinsic Factors Governing Fibroblast Cellular Identitymentioning
confidence: 99%
“…Considering that the diffusion range for Wnt antagonists is longer than that for ligands, at least during embryonic skin development 81 , it is plausible that adipocytes are primarily exposed to hair follicle-secreted Wnt antagonists. Furthermore, canonical Wnt signalling exerts indirect pro-adipogenic effects via epithelial skin cells 41,82 .…”
Section: Cyclic Remodelling Of Dwatmentioning
confidence: 99%
“…This tight control enables researchers to study the distinct cellular and signalling events in dermal adipose lineage with high temporal resolution. The fine microarchitecture of dWAT further enables investigators to precisely measure and detect the subtlest phenotypes presented as changes in layer thickness 6,41,45,46,80,82 . The level of phenotypic precision that dWAT affords researchers is not possible in other fat depots.…”
Section: Studying Adipose Lineage Developmentmentioning
confidence: 99%
“…In addition, dermal adipocytes secrete antimicrobial peptides to protect the skin from bacterial infection, thereby playing a role in the skin's innate immunity (Zhang et al 2015). Ectopic activation of β-catenin in the epithelial compartment affects several aspects of skin biology, including hair cycle, dermal fibroblasts, and adipose layer thickness (Deschene et al 2014;Donati et al 2014;Kretzschmar et al 2016;Lichtenberger et al 2016), suggesting that dermal changes are sensitive to alterations in the epithelial lineage. However, the physiologically relevant factor and the specific cell types governing the coordinated changes of dermal adipose layer and hair cycle progression remain unknown.…”
mentioning
confidence: 99%