p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation

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.
• 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.