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Title: Epidermal Wnt-B-catenin signaling regulates adipocyte differentiation via secretion of adipogenic factors.
Epworth Authors: Sinclair, Rodney
Other Authors: Donati, Giacomo
Proserpio, Valentina
Lichtenberger, Beate
Natsuga, Ken
Fujiwara, Hironobu
Watt, Fiona
Keywords: Head & Neck Clinical Institute, Epworth HealthCare, Victoria, Australia
Department of Dermatology, Epworth HealthCare, Richmond, Victoria, Australia.
Stem Cells
Receptor Cross-Talk
Stem Cell Niche
3T3-L1 Cells
Azo Compounds
Cell Differentiation
Cluster Analysis
Cell Biology
Flow Cytometry
Hair Follicle
Growth and Development
Wnt Signaling Pathway
beta Catenin
Oil Red O
Issue Date: Apr-2014
Publisher: United States National Academy of Sciences
Citation: Proceedings of the National Academy of Science U S A. 2014 Apr 15;111(15):E1501-9.
Abstract: It has long been recognized that the hair follicle growth cycle and oscillation in the thickness of the underlying adipocyte layer are synchronized. Although factors secreted by adipocytes are known to regulate the hair growth cycle, it is unclear whether the epidermis can regulate adipogenesis. We show that inhibition of epidermal Wnt/β-catenin signaling reduced adipocyte differentiation in developing and adult mouse dermis. Conversely, ectopic activation of epidermal Wnt signaling promoted adipocyte differentiation and hair growth. When the Wnt pathway was activated in the embryonic epidermis, there was a dramatic and premature increase in adipocytes in the absence of hair follicle formation, demonstrating that Wnt activation, rather than mature hair follicles, is required for adipocyte generation. Epidermal and dermal gene expression profiling identified keratinocyte-derived adipogenic factors that are induced by β-catenin activation. Wnt/β-catenin signaling-dependent secreted factors from keratinocytes promoted adipocyte differentiation in vitro, and we identified ligands for the bone morphogenetic protein and insulin pathways as proadipogenic factors. Our results indicate epidermal Wnt/β-catenin as a critical initiator of a signaling cascade that induces adipogenesis and highlight the role of epidermal Wnt signaling in synchronizing adipocyte differentiation with the hair growth cycle.
DOI: 10.1073/pnas.1312880111
PubMed URL:
ISSN: ‎0027-8424
Journal Title: Proceedings of the National Academy of Science U S A.
Type: Journal Article
Affiliated Organisations: Centre for Stem Cells and Regenerative Medicine, Kings College London, London, United Kingdom.
Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom.
European Bioinformatics Institute, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
University of Melbourne, Parkville, Victoria, Australia.
Laboratory for Tissue Microenvironment, RIKEN Center for Developmental Biology, Kobe, Hyogo, Japan.
Appears in Collections:Dermatology
Head & Neck

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