Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar

Johanna Laurikkala, Johanna Pispa, Hansung Jung, Pekka Nieminen, Marja Mikkola, Xiuping Wang, Ulpu Saarialho-Kere, Juan Galceran, Rudolf Grosschedl, Irma Thesleff

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

X-linked and autosomal forms of anhidrotic ectodermal dysplasia syndromes (HED) are characterized by deficient development of several ectodermal organs, including hair, teeth and exocrine glands. The recent cloning of the genes that underlie these syndromes, ectodysplasin (ED1) and the ectodysplasin A receptor (EDAR), and their identification as a novel TNF ligand-receptor pair suggested a role for TNF signaling in embryonic morphogenesis. In the mouse, the genes of the spontaneous mutations Tabby (Ta) and downless (dl) were identified as homologs of ED1 and EDAR, respectively. To gain insight into the function of this signaling pathway in development of skin and hair follicles, we analyzed the expression and regulation of Eda and Edar in wild type as well as Tabby and Lef1 mutant mouse embryos. We show that Eda and Edar expression is confined to the ectoderm and occurs in a pattern that suggests a role of ectodysplasin/Edar signaling in the interactions between the ectodermal compartments and the formation and function of hair placodes. By using skin explant cultures, we further show that this signaling pathway is intimately associated with interactions between the epithelial and mesenchymal tissues. We also find that Ta mutants lack completely the placodes of the first developing tylotrich hairs, and that they do not show patterned expression of placodal genes, including Bmp4, Lef1, Shh, Ptch and Edar, and the genes for β-catenin and activin A. Finally, we identified activin as a mesenchymal signal that stimulates Edar expression and WNT as a signal that induces Eda expression, suggesting a hierarchy of distinct signaling pathways in the development of skin and hair follicles. In conclusion, we suggest that Eda and Edar are associated with the onset of ectodermal patterning and that ectodysplasin/edar signaling also regulates the morphogenesis of hair follicles.

Original languageEnglish
Pages (from-to)2541-2553
Number of pages13
JournalDevelopment
Volume129
Issue number10
Publication statusPublished - 2002 Aug 20

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Ectodysplasin Receptors
Ectodysplasins
Hair Follicle
Hair
Morphogenesis
Skin
Tumor Necrosis Factors
Exocrine Glands
Genes
Ectodermal Dysplasia
Catenins
Activins
Ectoderm
Organism Cloning
Tooth
Embryonic Structures
Epithelium
Gene Expression
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Cite this

Laurikkala, J., Pispa, J., Jung, H., Nieminen, P., Mikkola, M., Wang, X., ... Thesleff, I. (2002). Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar. Development, 129(10), 2541-2553.
Laurikkala, Johanna ; Pispa, Johanna ; Jung, Hansung ; Nieminen, Pekka ; Mikkola, Marja ; Wang, Xiuping ; Saarialho-Kere, Ulpu ; Galceran, Juan ; Grosschedl, Rudolf ; Thesleff, Irma. / Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar. In: Development. 2002 ; Vol. 129, No. 10. pp. 2541-2553.
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Laurikkala, J, Pispa, J, Jung, H, Nieminen, P, Mikkola, M, Wang, X, Saarialho-Kere, U, Galceran, J, Grosschedl, R & Thesleff, I 2002, 'Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar', Development, vol. 129, no. 10, pp. 2541-2553.

Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar. / Laurikkala, Johanna; Pispa, Johanna; Jung, Hansung; Nieminen, Pekka; Mikkola, Marja; Wang, Xiuping; Saarialho-Kere, Ulpu; Galceran, Juan; Grosschedl, Rudolf; Thesleff, Irma.

In: Development, Vol. 129, No. 10, 20.08.2002, p. 2541-2553.

Research output: Contribution to journalArticle

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T1 - Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar

AU - Laurikkala, Johanna

AU - Pispa, Johanna

AU - Jung, Hansung

AU - Nieminen, Pekka

AU - Mikkola, Marja

AU - Wang, Xiuping

AU - Saarialho-Kere, Ulpu

AU - Galceran, Juan

AU - Grosschedl, Rudolf

AU - Thesleff, Irma

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N2 - X-linked and autosomal forms of anhidrotic ectodermal dysplasia syndromes (HED) are characterized by deficient development of several ectodermal organs, including hair, teeth and exocrine glands. The recent cloning of the genes that underlie these syndromes, ectodysplasin (ED1) and the ectodysplasin A receptor (EDAR), and their identification as a novel TNF ligand-receptor pair suggested a role for TNF signaling in embryonic morphogenesis. In the mouse, the genes of the spontaneous mutations Tabby (Ta) and downless (dl) were identified as homologs of ED1 and EDAR, respectively. To gain insight into the function of this signaling pathway in development of skin and hair follicles, we analyzed the expression and regulation of Eda and Edar in wild type as well as Tabby and Lef1 mutant mouse embryos. We show that Eda and Edar expression is confined to the ectoderm and occurs in a pattern that suggests a role of ectodysplasin/Edar signaling in the interactions between the ectodermal compartments and the formation and function of hair placodes. By using skin explant cultures, we further show that this signaling pathway is intimately associated with interactions between the epithelial and mesenchymal tissues. We also find that Ta mutants lack completely the placodes of the first developing tylotrich hairs, and that they do not show patterned expression of placodal genes, including Bmp4, Lef1, Shh, Ptch and Edar, and the genes for β-catenin and activin A. Finally, we identified activin as a mesenchymal signal that stimulates Edar expression and WNT as a signal that induces Eda expression, suggesting a hierarchy of distinct signaling pathways in the development of skin and hair follicles. In conclusion, we suggest that Eda and Edar are associated with the onset of ectodermal patterning and that ectodysplasin/edar signaling also regulates the morphogenesis of hair follicles.

AB - X-linked and autosomal forms of anhidrotic ectodermal dysplasia syndromes (HED) are characterized by deficient development of several ectodermal organs, including hair, teeth and exocrine glands. The recent cloning of the genes that underlie these syndromes, ectodysplasin (ED1) and the ectodysplasin A receptor (EDAR), and their identification as a novel TNF ligand-receptor pair suggested a role for TNF signaling in embryonic morphogenesis. In the mouse, the genes of the spontaneous mutations Tabby (Ta) and downless (dl) were identified as homologs of ED1 and EDAR, respectively. To gain insight into the function of this signaling pathway in development of skin and hair follicles, we analyzed the expression and regulation of Eda and Edar in wild type as well as Tabby and Lef1 mutant mouse embryos. We show that Eda and Edar expression is confined to the ectoderm and occurs in a pattern that suggests a role of ectodysplasin/Edar signaling in the interactions between the ectodermal compartments and the formation and function of hair placodes. By using skin explant cultures, we further show that this signaling pathway is intimately associated with interactions between the epithelial and mesenchymal tissues. We also find that Ta mutants lack completely the placodes of the first developing tylotrich hairs, and that they do not show patterned expression of placodal genes, including Bmp4, Lef1, Shh, Ptch and Edar, and the genes for β-catenin and activin A. Finally, we identified activin as a mesenchymal signal that stimulates Edar expression and WNT as a signal that induces Eda expression, suggesting a hierarchy of distinct signaling pathways in the development of skin and hair follicles. In conclusion, we suggest that Eda and Edar are associated with the onset of ectodermal patterning and that ectodysplasin/edar signaling also regulates the morphogenesis of hair follicles.

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Laurikkala J, Pispa J, Jung H, Nieminen P, Mikkola M, Wang X et al. Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar. Development. 2002 Aug 20;129(10):2541-2553.