p63 and the epithelial stem cell: more than status quo?
- Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
This extract was created in the absence of an 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).
Deduction of p63 function in epithelial morphogenesis. Schematic of epithelial morphogenesis in tissues expressing high levels of p63 in progenitor cell layers, including skin, breast, prostate, and urothelia. The steps where the process of epidermal development is blocked in p63-null mice were deduced separately by Mills et al. (1999) and Yang et al. (1999) as commitment and proliferative potential of stem cells, respectively.
p63 and epithelial morphogenesis—marker of progenitor cells?
Recent work by Koster et al. (2004) addresses the relationship between p63 and epithelial morphogenesis, and, by extension, the interface of stem cell biology and the origins of some of the most common forms of human cancers. Although the precise functional relationship between p63 and its illustrious cousin p53 in tumorigenesis remains the center of another debate (Yang et al. …
