p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation

Johanna Laurikkala, Marja L Mikkola, Martyn James, Mark Tummers, Alea A Mills, Irma Thesleff

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    Sammanfattning

    Heterozygous germline mutations in p63, a transcription factor of the p53 family, result in abnormal morphogenesis of the skin and its associated structures, including hair follicles and teeth. In mice lacking p63, all ectodermal organs fail to develop, and strati. cation of the epidermis is absent. We show that the ectodermal placodes that mark early tooth and hair follicle morphogenesis do not form in p63-deficient embryos, although the multilayered dental lamina that precedes tooth placode formation develops normally. The N-terminally truncated isoform of p63 (Delta Np63) was expressed at high levels in embryonic ectoderm at all stages of tooth and hair development, and it was already dominant over the transactivating TAp63 isoform prior to epidermal strati. cation. Bmp7, Fgfr2b, Jag1 and Notch1 transcripts were co-expressed with Delta Np63 in wild-type embryos, but were not detectable in the ectoderm of p63 mutants. In addition, beta-catenin and Edar transcripts were significantly reduced in skin ectoderm. We also demonstrate that BMP2, BMP7 and FGF10 are potent inducers of p63 in cultured tissue explants. Hence, we suggest that p63 regulates the morphogenesis of surface ectoderm and its derivatives via multiple signalling pathways.
    Originalspråkengelska
    TidskriftDevelopment
    Volym133
    Sidor (från-till)1553-1563
    Antal sidor11
    ISSN0950-1991
    DOI
    StatusPublicerad - 2006
    MoE-publikationstypA1 Tidskriftsartikel-refererad

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    title = "p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation",
    abstract = "Heterozygous germline mutations in p63, a transcription factor of the p53 family, result in abnormal morphogenesis of the skin and its associated structures, including hair follicles and teeth. In mice lacking p63, all ectodermal organs fail to develop, and strati. cation of the epidermis is absent. We show that the ectodermal placodes that mark early tooth and hair follicle morphogenesis do not form in p63-deficient embryos, although the multilayered dental lamina that precedes tooth placode formation develops normally. The N-terminally truncated isoform of p63 (Delta Np63) was expressed at high levels in embryonic ectoderm at all stages of tooth and hair development, and it was already dominant over the transactivating TAp63 isoform prior to epidermal strati. cation. Bmp7, Fgfr2b, Jag1 and Notch1 transcripts were co-expressed with Delta Np63 in wild-type embryos, but were not detectable in the ectoderm of p63 mutants. In addition, beta-catenin and Edar transcripts were significantly reduced in skin ectoderm. We also demonstrate that BMP2, BMP7 and FGF10 are potent inducers of p63 in cultured tissue explants. Hence, we suggest that p63 regulates the morphogenesis of surface ectoderm and its derivatives via multiple signalling pathways.",
    author = "Johanna Laurikkala and Mikkola, {Marja L} and Martyn James and Mark Tummers and Mills, {Alea A} and Irma Thesleff",
    year = "2006",
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    journal = "Development",
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    p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation. / Laurikkala, Johanna; Mikkola, Marja L; James, Martyn; Tummers, Mark; Mills, Alea A; Thesleff, Irma.

    I: Development, Vol. 133, 2006, s. 1553-1563.

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    TY - JOUR

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    AU - Laurikkala, Johanna

    AU - Mikkola, Marja L

    AU - James, Martyn

    AU - Tummers, Mark

    AU - Mills, Alea A

    AU - Thesleff, Irma

    PY - 2006

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    AB - Heterozygous germline mutations in p63, a transcription factor of the p53 family, result in abnormal morphogenesis of the skin and its associated structures, including hair follicles and teeth. In mice lacking p63, all ectodermal organs fail to develop, and strati. cation of the epidermis is absent. We show that the ectodermal placodes that mark early tooth and hair follicle morphogenesis do not form in p63-deficient embryos, although the multilayered dental lamina that precedes tooth placode formation develops normally. The N-terminally truncated isoform of p63 (Delta Np63) was expressed at high levels in embryonic ectoderm at all stages of tooth and hair development, and it was already dominant over the transactivating TAp63 isoform prior to epidermal strati. cation. Bmp7, Fgfr2b, Jag1 and Notch1 transcripts were co-expressed with Delta Np63 in wild-type embryos, but were not detectable in the ectoderm of p63 mutants. In addition, beta-catenin and Edar transcripts were significantly reduced in skin ectoderm. We also demonstrate that BMP2, BMP7 and FGF10 are potent inducers of p63 in cultured tissue explants. Hence, we suggest that p63 regulates the morphogenesis of surface ectoderm and its derivatives via multiple signalling pathways.

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