Ectodysplasin has a dual role in ectodermal organogenesis: inhibition of Bmp activity and induction of Shh expression

Marja Pummila, Ingrid Fliniaux, Risto Jaatinen, Martyn J James, Johanna Laurikkala, Pascal Schneider, Irma Thesleff, Marja L Mikkola

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    Sammanfattning

    Ectodermal organogenesis is regulated by inductive and reciprocal signalling cascades that involve multiple signal molecules in several conserved families. Ectodysplasin-A ( Eda), a tumour necrosis factor-like signalling molecule, and its receptor Edar are required for the development of a number of ectodermal organs in vertebrates. In mice, lack of Eda leads to failure in primary hair placode formation and missing or abnormally shaped teeth, whereas mice overexpressing Eda are characterized by enlarged hair placodes and supernumerary teeth and mammary glands. Here, we report two signalling outcomes of the Eda pathway: suppression of bone morphogenetic protein ( Bmp) activity and upregulation of sonic hedgehog (Shh) signalling. Recombinant Eda counteracted Bmp4 activity in developing teeth and, importantly, inhibition of BMP activity by exogenous noggin partially restored primary hair placode formation in Eda-deficient skin in vitro, indicating that suppression of Bmp activity was compromised in the absence of Eda. The downstream effects of the Eda pathway are likely to be mediated by transcription factor nuclear factor-kappa B (NF-kappa B), but the transcriptional targets of Edar have remained unknown. Using a quantitative approach, we show in cultured embryonic skin that Eda induced the expression of two Bmp inhibitors, Ccn2/Ctgf (CCN family protein 2/connective tissue growth factor) and follistatin. Moreover, our data indicate that Shh is a likely transcriptional target of Edar, but, unlike noggin, recombinant Shh was unable to rescue primary hair placode formation in Eda-deficient skin explants.
    Originalspråkengelska
    TidskriftDevelopment
    Volym134
    Sidor (från-till)117-125
    Antal sidor9
    ISSN0950-1991
    DOI
    StatusPublicerad - 2007
    MoE-publikationstypA1 Tidskriftsartikel-refererad

    Citera det här

    Pummila, Marja ; Fliniaux, Ingrid ; Jaatinen, Risto ; James, Martyn J ; Laurikkala, Johanna ; Schneider, Pascal ; Thesleff, Irma ; Mikkola, Marja L. / Ectodysplasin has a dual role in ectodermal organogenesis : inhibition of Bmp activity and induction of Shh expression. I: Development. 2007 ; Vol. 134. s. 117-125.
    @article{73c7e5d51c6e41c38568c121ee1fda89,
    title = "Ectodysplasin has a dual role in ectodermal organogenesis: inhibition of Bmp activity and induction of Shh expression",
    abstract = "Ectodermal organogenesis is regulated by inductive and reciprocal signalling cascades that involve multiple signal molecules in several conserved families. Ectodysplasin-A ( Eda), a tumour necrosis factor-like signalling molecule, and its receptor Edar are required for the development of a number of ectodermal organs in vertebrates. In mice, lack of Eda leads to failure in primary hair placode formation and missing or abnormally shaped teeth, whereas mice overexpressing Eda are characterized by enlarged hair placodes and supernumerary teeth and mammary glands. Here, we report two signalling outcomes of the Eda pathway: suppression of bone morphogenetic protein ( Bmp) activity and upregulation of sonic hedgehog (Shh) signalling. Recombinant Eda counteracted Bmp4 activity in developing teeth and, importantly, inhibition of BMP activity by exogenous noggin partially restored primary hair placode formation in Eda-deficient skin in vitro, indicating that suppression of Bmp activity was compromised in the absence of Eda. The downstream effects of the Eda pathway are likely to be mediated by transcription factor nuclear factor-kappa B (NF-kappa B), but the transcriptional targets of Edar have remained unknown. Using a quantitative approach, we show in cultured embryonic skin that Eda induced the expression of two Bmp inhibitors, Ccn2/Ctgf (CCN family protein 2/connective tissue growth factor) and follistatin. Moreover, our data indicate that Shh is a likely transcriptional target of Edar, but, unlike noggin, recombinant Shh was unable to rescue primary hair placode formation in Eda-deficient skin explants.",
    author = "Marja Pummila and Ingrid Fliniaux and Risto Jaatinen and James, {Martyn J} and Johanna Laurikkala and Pascal Schneider and Irma Thesleff and Mikkola, {Marja L}",
    year = "2007",
    doi = "10.1242/dev.02708",
    language = "English",
    volume = "134",
    pages = "117--125",
    journal = "Development",
    issn = "0950-1991",
    publisher = "Company of Biologists Ltd",

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    Ectodysplasin has a dual role in ectodermal organogenesis : inhibition of Bmp activity and induction of Shh expression. / Pummila, Marja; Fliniaux, Ingrid; Jaatinen, Risto; James, Martyn J; Laurikkala, Johanna; Schneider, Pascal; Thesleff, Irma; Mikkola, Marja L.

    I: Development, Vol. 134, 2007, s. 117-125.

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    TY - JOUR

    T1 - Ectodysplasin has a dual role in ectodermal organogenesis

    T2 - inhibition of Bmp activity and induction of Shh expression

    AU - Pummila, Marja

    AU - Fliniaux, Ingrid

    AU - Jaatinen, Risto

    AU - James, Martyn J

    AU - Laurikkala, Johanna

    AU - Schneider, Pascal

    AU - Thesleff, Irma

    AU - Mikkola, Marja L

    PY - 2007

    Y1 - 2007

    N2 - Ectodermal organogenesis is regulated by inductive and reciprocal signalling cascades that involve multiple signal molecules in several conserved families. Ectodysplasin-A ( Eda), a tumour necrosis factor-like signalling molecule, and its receptor Edar are required for the development of a number of ectodermal organs in vertebrates. In mice, lack of Eda leads to failure in primary hair placode formation and missing or abnormally shaped teeth, whereas mice overexpressing Eda are characterized by enlarged hair placodes and supernumerary teeth and mammary glands. Here, we report two signalling outcomes of the Eda pathway: suppression of bone morphogenetic protein ( Bmp) activity and upregulation of sonic hedgehog (Shh) signalling. Recombinant Eda counteracted Bmp4 activity in developing teeth and, importantly, inhibition of BMP activity by exogenous noggin partially restored primary hair placode formation in Eda-deficient skin in vitro, indicating that suppression of Bmp activity was compromised in the absence of Eda. The downstream effects of the Eda pathway are likely to be mediated by transcription factor nuclear factor-kappa B (NF-kappa B), but the transcriptional targets of Edar have remained unknown. Using a quantitative approach, we show in cultured embryonic skin that Eda induced the expression of two Bmp inhibitors, Ccn2/Ctgf (CCN family protein 2/connective tissue growth factor) and follistatin. Moreover, our data indicate that Shh is a likely transcriptional target of Edar, but, unlike noggin, recombinant Shh was unable to rescue primary hair placode formation in Eda-deficient skin explants.

    AB - Ectodermal organogenesis is regulated by inductive and reciprocal signalling cascades that involve multiple signal molecules in several conserved families. Ectodysplasin-A ( Eda), a tumour necrosis factor-like signalling molecule, and its receptor Edar are required for the development of a number of ectodermal organs in vertebrates. In mice, lack of Eda leads to failure in primary hair placode formation and missing or abnormally shaped teeth, whereas mice overexpressing Eda are characterized by enlarged hair placodes and supernumerary teeth and mammary glands. Here, we report two signalling outcomes of the Eda pathway: suppression of bone morphogenetic protein ( Bmp) activity and upregulation of sonic hedgehog (Shh) signalling. Recombinant Eda counteracted Bmp4 activity in developing teeth and, importantly, inhibition of BMP activity by exogenous noggin partially restored primary hair placode formation in Eda-deficient skin in vitro, indicating that suppression of Bmp activity was compromised in the absence of Eda. The downstream effects of the Eda pathway are likely to be mediated by transcription factor nuclear factor-kappa B (NF-kappa B), but the transcriptional targets of Edar have remained unknown. Using a quantitative approach, we show in cultured embryonic skin that Eda induced the expression of two Bmp inhibitors, Ccn2/Ctgf (CCN family protein 2/connective tissue growth factor) and follistatin. Moreover, our data indicate that Shh is a likely transcriptional target of Edar, but, unlike noggin, recombinant Shh was unable to rescue primary hair placode formation in Eda-deficient skin explants.

    U2 - 10.1242/dev.02708

    DO - 10.1242/dev.02708

    M3 - Article

    VL - 134

    SP - 117

    EP - 125

    JO - Development

    JF - Development

    SN - 0950-1991

    ER -