Identification of dkk4 as a target of Eda-A1/Edar pathway reveals an unexpected role of ectodysplasin as inhibitor of Wnt signalling in ectodermal placodes

Ingrid Fliniaux, Marja L Mikkola, Sylvie Lefebvre, Irma Thesleff

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    Sammanfattning

    The development of epithelial appendages, including hairs, glands and teeth starts from ectodermal placodes, and is regulated by interplay of stimulatory and inhibitory signals. Ectodysplasin-Al (Eda-Al) and Writs are high in hierarchy of placode activators. To identify direct targets of ectodysplasin pathway, we performed microarray profiling of genes differentially regulated by short exposure to recombinant Eda-Al in embryonic eda(+/+) skin explants. Surprisingly, there were only two genes with obvious involvement in Wnt pathway: dkk4 (most highly induced gene in the screen), and Irp4. Both genes colocalized with Eda-Al receptor Edar in placodes of ectodermal Organs. They were upregulated upon Edar activation while several other Writ associated genes previously suggested as Edar targets were unaffected. However, low dkk4 and Irp4 expression was retained in the absence of NF-kappa B signalling in eda(-/-) hair placodes. We provide evidence that this expression was dependent on Wnt activity present prior to Eda-Al/Edar signalling. Dkk4 was recently suggested as a key Writ antagonist regulating lateral inhibition essential for Correct patterning of hair follicles. Several pieces of evidence suggest Lrp4 as a Wnt inhibitor, as well. The finding that Eda-Al induces placorde inhibitors was unexpected, and underlines the importance of delicate fine-tuning of signalling during placode formation. (C) 2008 Elsevier Inc. All rights reserved.
    Originalspråkengelska
    TidskriftDevelopmental Biology
    Volym320
    Utgåva1
    Sidor (från-till)60-71
    Antal sidor12
    ISSN0012-1606
    DOI
    StatusPublicerad - 2008
    MoE-publikationstypA1 Tidskriftsartikel-refererad

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    title = "Identification of dkk4 as a target of Eda-A1/Edar pathway reveals an unexpected role of ectodysplasin as inhibitor of Wnt signalling in ectodermal placodes",
    abstract = "The development of epithelial appendages, including hairs, glands and teeth starts from ectodermal placodes, and is regulated by interplay of stimulatory and inhibitory signals. Ectodysplasin-Al (Eda-Al) and Writs are high in hierarchy of placode activators. To identify direct targets of ectodysplasin pathway, we performed microarray profiling of genes differentially regulated by short exposure to recombinant Eda-Al in embryonic eda(+/+) skin explants. Surprisingly, there were only two genes with obvious involvement in Wnt pathway: dkk4 (most highly induced gene in the screen), and Irp4. Both genes colocalized with Eda-Al receptor Edar in placodes of ectodermal Organs. They were upregulated upon Edar activation while several other Writ associated genes previously suggested as Edar targets were unaffected. However, low dkk4 and Irp4 expression was retained in the absence of NF-kappa B signalling in eda(-/-) hair placodes. We provide evidence that this expression was dependent on Wnt activity present prior to Eda-Al/Edar signalling. Dkk4 was recently suggested as a key Writ antagonist regulating lateral inhibition essential for Correct patterning of hair follicles. Several pieces of evidence suggest Lrp4 as a Wnt inhibitor, as well. The finding that Eda-Al induces placorde inhibitors was unexpected, and underlines the importance of delicate fine-tuning of signalling during placode formation. (C) 2008 Elsevier Inc. All rights reserved.",
    author = "Ingrid Fliniaux and Mikkola, {Marja L} and Sylvie Lefebvre and Irma Thesleff",
    year = "2008",
    doi = "10.1016/j.ydbio.2008.04.023",
    language = "English",
    volume = "320",
    pages = "60--71",
    journal = "Developmental Biology",
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    Identification of dkk4 as a target of Eda-A1/Edar pathway reveals an unexpected role of ectodysplasin as inhibitor of Wnt signalling in ectodermal placodes. / Fliniaux, Ingrid; Mikkola, Marja L; Lefebvre, Sylvie; Thesleff, Irma.

    I: Developmental Biology, Vol. 320, Nr. 1, 2008, s. 60-71.

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    TY - JOUR

    T1 - Identification of dkk4 as a target of Eda-A1/Edar pathway reveals an unexpected role of ectodysplasin as inhibitor of Wnt signalling in ectodermal placodes

    AU - Fliniaux, Ingrid

    AU - Mikkola, Marja L

    AU - Lefebvre, Sylvie

    AU - Thesleff, Irma

    PY - 2008

    Y1 - 2008

    N2 - The development of epithelial appendages, including hairs, glands and teeth starts from ectodermal placodes, and is regulated by interplay of stimulatory and inhibitory signals. Ectodysplasin-Al (Eda-Al) and Writs are high in hierarchy of placode activators. To identify direct targets of ectodysplasin pathway, we performed microarray profiling of genes differentially regulated by short exposure to recombinant Eda-Al in embryonic eda(+/+) skin explants. Surprisingly, there were only two genes with obvious involvement in Wnt pathway: dkk4 (most highly induced gene in the screen), and Irp4. Both genes colocalized with Eda-Al receptor Edar in placodes of ectodermal Organs. They were upregulated upon Edar activation while several other Writ associated genes previously suggested as Edar targets were unaffected. However, low dkk4 and Irp4 expression was retained in the absence of NF-kappa B signalling in eda(-/-) hair placodes. We provide evidence that this expression was dependent on Wnt activity present prior to Eda-Al/Edar signalling. Dkk4 was recently suggested as a key Writ antagonist regulating lateral inhibition essential for Correct patterning of hair follicles. Several pieces of evidence suggest Lrp4 as a Wnt inhibitor, as well. The finding that Eda-Al induces placorde inhibitors was unexpected, and underlines the importance of delicate fine-tuning of signalling during placode formation. (C) 2008 Elsevier Inc. All rights reserved.

    AB - The development of epithelial appendages, including hairs, glands and teeth starts from ectodermal placodes, and is regulated by interplay of stimulatory and inhibitory signals. Ectodysplasin-Al (Eda-Al) and Writs are high in hierarchy of placode activators. To identify direct targets of ectodysplasin pathway, we performed microarray profiling of genes differentially regulated by short exposure to recombinant Eda-Al in embryonic eda(+/+) skin explants. Surprisingly, there were only two genes with obvious involvement in Wnt pathway: dkk4 (most highly induced gene in the screen), and Irp4. Both genes colocalized with Eda-Al receptor Edar in placodes of ectodermal Organs. They were upregulated upon Edar activation while several other Writ associated genes previously suggested as Edar targets were unaffected. However, low dkk4 and Irp4 expression was retained in the absence of NF-kappa B signalling in eda(-/-) hair placodes. We provide evidence that this expression was dependent on Wnt activity present prior to Eda-Al/Edar signalling. Dkk4 was recently suggested as a key Writ antagonist regulating lateral inhibition essential for Correct patterning of hair follicles. Several pieces of evidence suggest Lrp4 as a Wnt inhibitor, as well. The finding that Eda-Al induces placorde inhibitors was unexpected, and underlines the importance of delicate fine-tuning of signalling during placode formation. (C) 2008 Elsevier Inc. All rights reserved.

    U2 - 10.1016/j.ydbio.2008.04.023

    DO - 10.1016/j.ydbio.2008.04.023

    M3 - Article

    VL - 320

    SP - 60

    EP - 71

    JO - Developmental Biology

    JF - Developmental Biology

    SN - 0012-1606

    IS - 1

    ER -