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: To identify the cause of cleft palate, we analyzed the p63+/L514F mouse oral cavity during development. At embryonic day (E)13.5, although reproducibly smaller, the mutant palatal shelves pointed downwards on either side of the tongue similar to their wild-type littermates (Fig 2A, C and D). Although the mutant palatal shelves elevated appropriately at E14.5, they were smaller, widely spaced and failed to meet in the midline (Fig 2B).