Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair.
The mouse hair coat comprises protective "primary" and thermo-regulatory "secondary" hairs. Primary hair formation is ectodysplasin (Eda) dependent, but it has been puzzling that Tabby (Eda(-/y)) mice still make secondary hair. We report that Dickkopf 4 (Dkk4), a Wnt antagonist, affects an auxiliary pathway for Eda-independent development of secondary hair. A Dkk4 transgene in wild-type mice had no effect on primary hair, but secondary hairs were severely malformed. Dkk4 action on secondary hair was further demonstrated when the transgene was introduced into Tabby mice: the usual secondary follicle induction was completely blocked. The Dkk4-regulated secondary hair pathway, like the Eda-dependent primary hair pathway, is further mediated by selective activation of Shh. The results thus reveal two complex molecular pathways that distinctly regulate subtype-based morphogenesis of hair follicles, and provide a resolution for the longstanding puzzle of hair formation in Tabby mice lacking Eda.
Cui
Chang-Yi
CY
Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.
Kunisada
Makoto
M
Piao
Yulan
Y
Childress
Victoria
V
Ko
Minoru S H
MS
Schlessinger
David
D
D000818:Animals; D053331:Ectodysplasins / Q000502:physiology*; D006197:Hair / Q000254:growth & development*; D018859:Hair Follicle / Q000254:growth & development; D053823:Hedgehog Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009024:Morphogenesis
C513131:Dkk4 protein, mouse; D053331:Ectodysplasins; C506019:Eda protein, mouse; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins; C465570:Shh protein, mouse
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