p63 and the epithelial stem cell: more than status quo?

Abstract

The discovery of p63, the most ancient member of the p53 family (for review, see Yang et al. 2002), was soon followed by back-to-back reports of a remarkable phenotype of mice lacking this gene: They die perinatally due to the absence of a large number of epithelial structures including skin, breast, prostate, and urothelia, among others (Mills et al. 1999; Yang et al. 1999). Despite the contemporaneous nature of these publications, they expressed profound disagreement regarding the function of p63, as reflected in the mouse mutants. Mills et al. (1999) argued that p63 was essential for the commitment of a simple ectoderm to epidermal lineages, whereas Yang et al. (1999) argued that commitment and differentiation of the ectoderm were essentially intact in these mice, and that what was defective was the “proliferative potential” of the epithelial stem cells (Fig. 1). Principals from the first group have now addressed this problem from fundamentally different angles and have proposed new and unexpected functions of the p63 gene in epithelial commitment, maintenance, and differentiation (Koster et al. 2004).