Epidermal Wnt/β-catenin signaling regulates adipocyte differentiation via secretion of adipogenic factors.
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.
Centre for Stem Cells and Regenerative Medicine, Kings College London, London SE1 9RT, United Kingdom.
Giacomo
G
Donati
Valentina
V
Proserpio
Beate Maria
BM
Lichtenberger
Ken
K
Natsuga
Rodney
R
Sinclair
Hironobu
H
Fujiwara
Fiona M
FM
Watt
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D001391:Azo Compounds; D002454:Cell Differentiation / Q000502:physiology*; D016000:Cluster Analysis; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D005434:Flow Cytometry; D018859:Hair Follicle / Q000254:growth & development*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
D001391:Azo Compounds; D051176:beta Catenin; C011049:oil red O
niche cross-talk; skin; stem cells