Activation of β-catenin signaling programs embryonic epidermis to hair follicle fate

Yuhang Zhang, Thomas Andl, Steven H. Yang, Monica Teta, Fei Liu, John T. Seykora, John W. Tobias, Stefano Piccolo, Ruth Schmidt-Ullrich, Andras Nagy, Makoto M. Taketo, Andrzej A. Dlugosz, Sarah E. Millar

Research output: Contribution to journalArticleResearchpeer-review

Abstract

β-Catenin signaling is required for hair follicle development, but it is unknown whether its activation is sufficient to globally program embryonic epidermis to hair follicle fate. To address this, we mutated endogenous epithelial β-catenin to a dominant-active form in vivo. Hair follicle placodes were expanded and induced prematurely in activated β-catenin mutant embryos, but failed to invaginate or form multilayered structures. Eventually, the entire epidermis adopted hair follicle fate, broadly expressing hair shaft keratins in place of epidermal stratification proteins. Mutant embryonic skin was precociously innervated, and displayed prenatal pigmentation, a phenomenon never observed in wild-type controls. Thus, β-catenin signaling programs the epidermis towards placode and hair shaft fate at the expense of epidermal differentiation, and activates signals directing pigmentation and innervation. In transcript profiling experiments, we identified elevated expression of Sp5, a direct β-catenin target and transcriptional repressor. We show that Sp5 normally localizes to hair follicle placodes and can suppress epidermal differentiation gene expression. We identified the pigmentation regulators Foxn1, Adamts20 and Kiti, and the neural guidance genes Sema4c, Sema3c, Unc5b and Unc5c, as potential mediators of the effects of β-catenin signaling on pigmentation and innervation. Our data provide evidence for a new paradigm in which, in addition to promoting hair follicle placode and hair shaft fate, β-catenin signaling actively suppresses epidermal differentiation and directs pigmentation and nerve fiber growth. Controlled downregulation of β-catenin signaling is required for normal placode patterning within embryonic ectoderm, hair follicle downgrowth, and adoption of the full range of follicular fates.

Original languageEnglish
Pages (from-to)2161-2172
Number of pages12
JournalDevelopment
Volume135
Issue number12
DOIs
Publication statusPublished - Jun 2008
Externally publishedYes

Keywords

  • β-catenin
  • Epidermis
  • Hair follicle
  • Mouse embryo
  • Wnt

Cite this

Zhang, Y., Andl, T., Yang, S. H., Teta, M., Liu, F., Seykora, J. T., ... Millar, S. E. (2008). Activation of β-catenin signaling programs embryonic epidermis to hair follicle fate. Development, 135(12), 2161-2172. https://doi.org/10.1242/dev.017459
Zhang, Yuhang ; Andl, Thomas ; Yang, Steven H. ; Teta, Monica ; Liu, Fei ; Seykora, John T. ; Tobias, John W. ; Piccolo, Stefano ; Schmidt-Ullrich, Ruth ; Nagy, Andras ; Taketo, Makoto M. ; Dlugosz, Andrzej A. ; Millar, Sarah E. / Activation of β-catenin signaling programs embryonic epidermis to hair follicle fate. In: Development. 2008 ; Vol. 135, No. 12. pp. 2161-2172.
@article{740202cca6474f958117fa751b2e6b10,
title = "Activation of β-catenin signaling programs embryonic epidermis to hair follicle fate",
abstract = "β-Catenin signaling is required for hair follicle development, but it is unknown whether its activation is sufficient to globally program embryonic epidermis to hair follicle fate. To address this, we mutated endogenous epithelial β-catenin to a dominant-active form in vivo. Hair follicle placodes were expanded and induced prematurely in activated β-catenin mutant embryos, but failed to invaginate or form multilayered structures. Eventually, the entire epidermis adopted hair follicle fate, broadly expressing hair shaft keratins in place of epidermal stratification proteins. Mutant embryonic skin was precociously innervated, and displayed prenatal pigmentation, a phenomenon never observed in wild-type controls. Thus, β-catenin signaling programs the epidermis towards placode and hair shaft fate at the expense of epidermal differentiation, and activates signals directing pigmentation and innervation. In transcript profiling experiments, we identified elevated expression of Sp5, a direct β-catenin target and transcriptional repressor. We show that Sp5 normally localizes to hair follicle placodes and can suppress epidermal differentiation gene expression. We identified the pigmentation regulators Foxn1, Adamts20 and Kiti, and the neural guidance genes Sema4c, Sema3c, Unc5b and Unc5c, as potential mediators of the effects of β-catenin signaling on pigmentation and innervation. Our data provide evidence for a new paradigm in which, in addition to promoting hair follicle placode and hair shaft fate, β-catenin signaling actively suppresses epidermal differentiation and directs pigmentation and nerve fiber growth. Controlled downregulation of β-catenin signaling is required for normal placode patterning within embryonic ectoderm, hair follicle downgrowth, and adoption of the full range of follicular fates.",
keywords = "β-catenin, Epidermis, Hair follicle, Mouse embryo, Wnt",
author = "Yuhang Zhang and Thomas Andl and Yang, {Steven H.} and Monica Teta and Fei Liu and Seykora, {John T.} and Tobias, {John W.} and Stefano Piccolo and Ruth Schmidt-Ullrich and Andras Nagy and Taketo, {Makoto M.} and Dlugosz, {Andrzej A.} and Millar, {Sarah E.}",
year = "2008",
month = "6",
doi = "10.1242/dev.017459",
language = "English",
volume = "135",
pages = "2161--2172",
journal = "Development",
issn = "0950-1991",
publisher = "The Company of Biologists Ltd",
number = "12",

}

Zhang, Y, Andl, T, Yang, SH, Teta, M, Liu, F, Seykora, JT, Tobias, JW, Piccolo, S, Schmidt-Ullrich, R, Nagy, A, Taketo, MM, Dlugosz, AA & Millar, SE 2008, 'Activation of β-catenin signaling programs embryonic epidermis to hair follicle fate' Development, vol. 135, no. 12, pp. 2161-2172. https://doi.org/10.1242/dev.017459

Activation of β-catenin signaling programs embryonic epidermis to hair follicle fate. / Zhang, Yuhang; Andl, Thomas; Yang, Steven H.; Teta, Monica; Liu, Fei; Seykora, John T.; Tobias, John W.; Piccolo, Stefano; Schmidt-Ullrich, Ruth; Nagy, Andras; Taketo, Makoto M.; Dlugosz, Andrzej A.; Millar, Sarah E.

In: Development, Vol. 135, No. 12, 06.2008, p. 2161-2172.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Activation of β-catenin signaling programs embryonic epidermis to hair follicle fate

AU - Zhang, Yuhang

AU - Andl, Thomas

AU - Yang, Steven H.

AU - Teta, Monica

AU - Liu, Fei

AU - Seykora, John T.

AU - Tobias, John W.

AU - Piccolo, Stefano

AU - Schmidt-Ullrich, Ruth

AU - Nagy, Andras

AU - Taketo, Makoto M.

AU - Dlugosz, Andrzej A.

AU - Millar, Sarah E.

PY - 2008/6

Y1 - 2008/6

N2 - β-Catenin signaling is required for hair follicle development, but it is unknown whether its activation is sufficient to globally program embryonic epidermis to hair follicle fate. To address this, we mutated endogenous epithelial β-catenin to a dominant-active form in vivo. Hair follicle placodes were expanded and induced prematurely in activated β-catenin mutant embryos, but failed to invaginate or form multilayered structures. Eventually, the entire epidermis adopted hair follicle fate, broadly expressing hair shaft keratins in place of epidermal stratification proteins. Mutant embryonic skin was precociously innervated, and displayed prenatal pigmentation, a phenomenon never observed in wild-type controls. Thus, β-catenin signaling programs the epidermis towards placode and hair shaft fate at the expense of epidermal differentiation, and activates signals directing pigmentation and innervation. In transcript profiling experiments, we identified elevated expression of Sp5, a direct β-catenin target and transcriptional repressor. We show that Sp5 normally localizes to hair follicle placodes and can suppress epidermal differentiation gene expression. We identified the pigmentation regulators Foxn1, Adamts20 and Kiti, and the neural guidance genes Sema4c, Sema3c, Unc5b and Unc5c, as potential mediators of the effects of β-catenin signaling on pigmentation and innervation. Our data provide evidence for a new paradigm in which, in addition to promoting hair follicle placode and hair shaft fate, β-catenin signaling actively suppresses epidermal differentiation and directs pigmentation and nerve fiber growth. Controlled downregulation of β-catenin signaling is required for normal placode patterning within embryonic ectoderm, hair follicle downgrowth, and adoption of the full range of follicular fates.

AB - β-Catenin signaling is required for hair follicle development, but it is unknown whether its activation is sufficient to globally program embryonic epidermis to hair follicle fate. To address this, we mutated endogenous epithelial β-catenin to a dominant-active form in vivo. Hair follicle placodes were expanded and induced prematurely in activated β-catenin mutant embryos, but failed to invaginate or form multilayered structures. Eventually, the entire epidermis adopted hair follicle fate, broadly expressing hair shaft keratins in place of epidermal stratification proteins. Mutant embryonic skin was precociously innervated, and displayed prenatal pigmentation, a phenomenon never observed in wild-type controls. Thus, β-catenin signaling programs the epidermis towards placode and hair shaft fate at the expense of epidermal differentiation, and activates signals directing pigmentation and innervation. In transcript profiling experiments, we identified elevated expression of Sp5, a direct β-catenin target and transcriptional repressor. We show that Sp5 normally localizes to hair follicle placodes and can suppress epidermal differentiation gene expression. We identified the pigmentation regulators Foxn1, Adamts20 and Kiti, and the neural guidance genes Sema4c, Sema3c, Unc5b and Unc5c, as potential mediators of the effects of β-catenin signaling on pigmentation and innervation. Our data provide evidence for a new paradigm in which, in addition to promoting hair follicle placode and hair shaft fate, β-catenin signaling actively suppresses epidermal differentiation and directs pigmentation and nerve fiber growth. Controlled downregulation of β-catenin signaling is required for normal placode patterning within embryonic ectoderm, hair follicle downgrowth, and adoption of the full range of follicular fates.

KW - β-catenin

KW - Epidermis

KW - Hair follicle

KW - Mouse embryo

KW - Wnt

UR - http://www.scopus.com/inward/record.url?scp=47649092996&partnerID=8YFLogxK

U2 - 10.1242/dev.017459

DO - 10.1242/dev.017459

M3 - Article

VL - 135

SP - 2161

EP - 2172

JO - Development

JF - Development

SN - 0950-1991

IS - 12

ER -

Zhang Y, Andl T, Yang SH, Teta M, Liu F, Seykora JT et al. Activation of β-catenin signaling programs embryonic epidermis to hair follicle fate. Development. 2008 Jun;135(12):2161-2172. https://doi.org/10.1242/dev.017459