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Related Experiment Videos

p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation.

Johanna Laurikkala1, Marja L Mikkola, Martyn James

  • 1Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland.

Development (Cambridge, England)
|March 10, 2006
PubMed
Summary
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Germline mutations in p63 (a transcription factor) disrupt skin and ectodermal organ development, including hair and teeth. p63 is crucial for early morphogenesis, regulating signaling pathways essential for these structures.

Area of Science:

  • Developmental biology
  • Molecular genetics
  • Cell signaling

Background:

  • p63 is a transcription factor crucial for skin and ectodermal organ development.
  • Mutations in p63 lead to abnormal morphogenesis of skin appendages like hair follicles and teeth.
  • p63 deficiency in mice results in the failure of ectodermal organ development and epidermal stratification.

Purpose of the Study:

  • To investigate the role of p63 in the morphogenesis of ectodermal appendages, specifically teeth and hair follicles.
  • To identify signaling pathways regulated by p63 during embryonic development.
  • To understand the function of p63 isoforms, particularly DeltaNp63, in ectodermal development.

Main Methods:

  • Analysis of p63-deficient mouse embryos to observe developmental defects.

Related Experiment Videos

  • Gene expression analysis (e.g., Bmp7, Fgfr2b, Jag1, Notch1, beta-catenin, Edar) in wild-type and mutant embryos.
  • In vitro studies using cultured tissue explants to assess the inductive effects of BMP2, BMP7, and FGF10 on p63 expression.
  • Main Results:

    • Ectodermal placodes for tooth and hair follicle morphogenesis failed to form in p63-deficient embryos.
    • The DeltaNp63 isoform was highly expressed in embryonic ectoderm and dominant over TAp63.
    • Key signaling molecule transcripts (Bmp7, Fgfr2b, Jag1, Notch1, beta-catenin, Edar) were downregulated in p63 mutant ectoderm.
    • BMP2, BMP7, and FGF10 were identified as potent inducers of p63 in cultured tissues.

    Conclusions:

    • p63 plays a critical role in the formation of ectodermal placodes necessary for tooth and hair development.
    • The DeltaNp63 isoform is important for regulating early ectodermal morphogenesis.
    • p63 functions through multiple signaling pathways, including BMP and FGF signaling, to control the morphogenesis of surface ectoderm and its derivatives.