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Dev Biol
2014 Mar 15;3872:167-78. doi: 10.1016/j.ydbio.2014.01.010.
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Dkk2/Frzb in the dermal papillae regulates feather regeneration.
Chu Q
,
Cai L
,
Fu Y
,
Chen X
,
Yan Z
,
Lin X
,
Zhou G
,
Han H
,
Widelitz RB
,
Chuong CM
,
Wu W
,
Yue Z
.
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Avian feathers have robust growth and regeneration capability. To evaluate the contribution of signaling molecules and pathways in these processes, we profiled gene expression in the feather follicle using an absolute quantification approach. We identified hundreds of genes that mark specific components of the feather follicle: the dermal papillae (DP) which controls feather regeneration and axis formation, the pulp mesenchyme (Pp) which is derived from DP cells and nourishes the feather follicle, and the ramogenic zone epithelium (Erz) where a feather starts to branch. The feather DP is enriched in BMP/TGF-β signaling molecules and inhibitors for Wnt signaling including Dkk2/Frzb. Wnt ligands are mainly expressed in the feather epithelium and pulp. We find that while Wnt signaling is required for the maintenance of DP marker gene expression and feather regeneration, excessive Wnt signaling delays regeneration and reduces pulp formation. Manipulating Dkk2/Frzb expression by lentiviral-mediated overexpression, shRNA-knockdown, or by antibody neutralization resulted in dual feather axes formation. Our results suggest that the Wnt signaling in the proximal feather follicle is fine-tuned to accommodate feather regeneration and axis formation.
Fig. 3. Dkk2/Frzb antagonizes Wnt signaling.(A) Wnt reporter assay in HEK293T cells. Super-TOPFLASH,a Wnt responsive reporter was co-transfected into HEK293T cells together with Wnt1 and other plasmids as indicated.hDkk1 (human Dkk1) was used as a positive control.Fold induction of Wnt reporter activity is shown. The numbers for each gene indicates the amount of DNA transfected; total amount of DNA transfected in each well was 150ng, adjusted with pCS2þ plasmid.
(B) Anteriorization of Xenopus embryos by injected mRNAs as indicated. mRNAs of chicken Dkk2 (1ng per embryo), Dkk3 (6ng per embryo) or Frzb (2ng per embryo) were injected at 4-cell stage.The numbers of embryos with indicated phenotypes are also shown.(3/33) stands for 3 out of 33 injected embryos showed indicated phenotype.Control animals were injected with 250pg mRNA of preprolectin gene. (C) Summary of the Xenopus injection experiment.
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