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Adenovirus-mediated Wnt5a expression inhibits the telogen-to-anagen transition of hair follicles in mice.

Xing YZ, Wang RM, Yang K, Guo HY, Deng F, Li YH, Ye JX, He L, Lian XH, Yang T - Int J Med Sci (2013)

Bottom Line: However, following an extended period of time, four pelage hair types grew from hairless skin that was induced by Wnt5a, and the structure of these new hair shafts was normal.Using microarray analysis and quantitative arrays, we showed that the expression of β-catenin and some target genes of canonical Wnt signaling decreased after Wnt5a treatment.These data demonstrate that Wnt5a may inhibit the telogen stage to maintain a quiescent state of the hair follicle.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.

ABSTRACT
The canonical Wnt/β-catenin pathway plays an important role in hair cycle induction. Wnt5a is a non-canonical Wnt family member that generally antagonizes canonical Wnt signaling in other systems. In hair follicles, Wnt5a and canonical Wnt are both expressed in cells in the telogen stage. Wnt5a has been shown to be critical for controlling hair cell fate. However, the role that Wnt5a plays in the transition from the telogen to anagen stage is unknown. In this study, using whole-mount in situ hybridization, we show that Wnt5a is produced by several other cell types, excluding dermal papilla cells, throughout the hair cycle. For example, Wnt5a is expressed in bulge and secondary hair germ cells in the telogen stage. Our studies focused on the depilated 8-week-old mouse as a synchronized model of hair growth. Interestingly, overexpression of adenovirus Wnt5a in the dorsal skin of mice led to the elongation of the telogen stage and inhibition of the initiation of the anagen stage. However, following an extended period of time, four pelage hair types grew from hairless skin that was induced by Wnt5a, and the structure of these new hair shafts was normal. Using microarray analysis and quantitative arrays, we showed that the expression of β-catenin and some target genes of canonical Wnt signaling decreased after Wnt5a treatment. These data demonstrate that Wnt5a may inhibit the telogen stage to maintain a quiescent state of the hair follicle.

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Morphological comparison in pelage hair after treatment with Ad-Wnt5a-GFP. (A) Wnt5a staining after Ad-Wnt5a-GFP treatment (brown). (B) Hematoxylin and eosin staining of dP7 skin after Ad-GFP or Ad-Wnt5a-GFP treatment. Arrows indicate the central region of injection. GFP staining was shown in the insert. (C) Four pelage hair types were present in the Ad-Wnt5a-GFP group. (D) Hair shaft from the Ad-Wnt5a-GFP group was examined by light microscopy and SEM. Bar=50 μm.
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Figure 3: Morphological comparison in pelage hair after treatment with Ad-Wnt5a-GFP. (A) Wnt5a staining after Ad-Wnt5a-GFP treatment (brown). (B) Hematoxylin and eosin staining of dP7 skin after Ad-GFP or Ad-Wnt5a-GFP treatment. Arrows indicate the central region of injection. GFP staining was shown in the insert. (C) Four pelage hair types were present in the Ad-Wnt5a-GFP group. (D) Hair shaft from the Ad-Wnt5a-GFP group was examined by light microscopy and SEM. Bar=50 μm.

Mentions: Depilation immediately induces the anagen phase of the hair cycle. Following depilation (7 days or dP7), the control (data not shown) and Ad-GFP-treated group (Fig. 2A, upper row) contained HFs that had entered the mid-anagen phase, as detected by a color change from pink to gray. The back skin of the mice was uniformly black by dP10, and hairs grew out of the skin surface at dP14. However, the skin still remained pink at dP7 in mice belonging to the group that was injected with Ad-Wnt5a-GFP (Fig. 2A, lower row), and the injection boundary in these mice was observed. The entire back skin was black by dP10 with the exception of the treated area, which was still smooth and pink. At dP14, hairs grew from the surface of the surrounding normal skin, but no hair grew from the treated skin. The round, hairless region on these mice slowly and gradually entered the anagen phase beginning at the periphery of the region and moving toward the center in a centripetal manner. The initiation of the anagen phase was accompanied by a change in skin color from pink to black. These results were reproducible over multiple experiments. We examined the expression of GFP in the treated samples at different time points, which means extrinsic Wnt5a. As time went on, its expression level would decreased, which could partly explain the attenuation of inhibition effect. We also injected Ad-Wnt5a-GFP at four different sites in the same mouse and observed the same inhibited phenotype (Fig. 2B). Staining for Wnt5a after Ad-Wnt5a-GFP treatment is shown in Fig. 3A.


Adenovirus-mediated Wnt5a expression inhibits the telogen-to-anagen transition of hair follicles in mice.

Xing YZ, Wang RM, Yang K, Guo HY, Deng F, Li YH, Ye JX, He L, Lian XH, Yang T - Int J Med Sci (2013)

Morphological comparison in pelage hair after treatment with Ad-Wnt5a-GFP. (A) Wnt5a staining after Ad-Wnt5a-GFP treatment (brown). (B) Hematoxylin and eosin staining of dP7 skin after Ad-GFP or Ad-Wnt5a-GFP treatment. Arrows indicate the central region of injection. GFP staining was shown in the insert. (C) Four pelage hair types were present in the Ad-Wnt5a-GFP group. (D) Hair shaft from the Ad-Wnt5a-GFP group was examined by light microscopy and SEM. Bar=50 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675505&req=5

Figure 3: Morphological comparison in pelage hair after treatment with Ad-Wnt5a-GFP. (A) Wnt5a staining after Ad-Wnt5a-GFP treatment (brown). (B) Hematoxylin and eosin staining of dP7 skin after Ad-GFP or Ad-Wnt5a-GFP treatment. Arrows indicate the central region of injection. GFP staining was shown in the insert. (C) Four pelage hair types were present in the Ad-Wnt5a-GFP group. (D) Hair shaft from the Ad-Wnt5a-GFP group was examined by light microscopy and SEM. Bar=50 μm.
Mentions: Depilation immediately induces the anagen phase of the hair cycle. Following depilation (7 days or dP7), the control (data not shown) and Ad-GFP-treated group (Fig. 2A, upper row) contained HFs that had entered the mid-anagen phase, as detected by a color change from pink to gray. The back skin of the mice was uniformly black by dP10, and hairs grew out of the skin surface at dP14. However, the skin still remained pink at dP7 in mice belonging to the group that was injected with Ad-Wnt5a-GFP (Fig. 2A, lower row), and the injection boundary in these mice was observed. The entire back skin was black by dP10 with the exception of the treated area, which was still smooth and pink. At dP14, hairs grew from the surface of the surrounding normal skin, but no hair grew from the treated skin. The round, hairless region on these mice slowly and gradually entered the anagen phase beginning at the periphery of the region and moving toward the center in a centripetal manner. The initiation of the anagen phase was accompanied by a change in skin color from pink to black. These results were reproducible over multiple experiments. We examined the expression of GFP in the treated samples at different time points, which means extrinsic Wnt5a. As time went on, its expression level would decreased, which could partly explain the attenuation of inhibition effect. We also injected Ad-Wnt5a-GFP at four different sites in the same mouse and observed the same inhibited phenotype (Fig. 2B). Staining for Wnt5a after Ad-Wnt5a-GFP treatment is shown in Fig. 3A.

Bottom Line: However, following an extended period of time, four pelage hair types grew from hairless skin that was induced by Wnt5a, and the structure of these new hair shafts was normal.Using microarray analysis and quantitative arrays, we showed that the expression of β-catenin and some target genes of canonical Wnt signaling decreased after Wnt5a treatment.These data demonstrate that Wnt5a may inhibit the telogen stage to maintain a quiescent state of the hair follicle.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.

ABSTRACT
The canonical Wnt/β-catenin pathway plays an important role in hair cycle induction. Wnt5a is a non-canonical Wnt family member that generally antagonizes canonical Wnt signaling in other systems. In hair follicles, Wnt5a and canonical Wnt are both expressed in cells in the telogen stage. Wnt5a has been shown to be critical for controlling hair cell fate. However, the role that Wnt5a plays in the transition from the telogen to anagen stage is unknown. In this study, using whole-mount in situ hybridization, we show that Wnt5a is produced by several other cell types, excluding dermal papilla cells, throughout the hair cycle. For example, Wnt5a is expressed in bulge and secondary hair germ cells in the telogen stage. Our studies focused on the depilated 8-week-old mouse as a synchronized model of hair growth. Interestingly, overexpression of adenovirus Wnt5a in the dorsal skin of mice led to the elongation of the telogen stage and inhibition of the initiation of the anagen stage. However, following an extended period of time, four pelage hair types grew from hairless skin that was induced by Wnt5a, and the structure of these new hair shafts was normal. Using microarray analysis and quantitative arrays, we showed that the expression of β-catenin and some target genes of canonical Wnt signaling decreased after Wnt5a treatment. These data demonstrate that Wnt5a may inhibit the telogen stage to maintain a quiescent state of the hair follicle.

Show MeSH
Related in: MedlinePlus