Mutant p63 causes defective expansion of ectodermal progenitor cells and impaired FGF signalling in AEC syndrome.
Bottom Line: The AEC mutation exerts a selective dominant-negative function on wild-type p63 by affecting progenitor cell expansion during ectodermal development leading to a defective epidermal stem cell compartment.These phenotypes are associated with impairment of fibroblast growth factor (FGF) signalling resulting from reduced expression of Fgfr2 and Fgfr3, direct p63 target genes.Restoring Fgfr2b expression in p63(+/L514F) epithelial cells by treatment with FGF7 reactivates downstream mitogen-activated protein kinase signalling and cell proliferation.
Affiliation: Fondazione IRCCS SDN, Napoli, Italy.Show MeSH
Related in: MedlinePlus
Mentions: Severe hypoplasia was also observed in p63+/L514F epidermis (40% thinner than wild-type) during embryonic development and at birth, with a reduction in the number of nuclei and a more flattened appearance of cells in all layers (Fig 3A and B). In contrast, no hypoplasia was observed in epidermis of mice heterozygous for a mutation in p63 (p63+/−) (Supporting Information Fig S4A).