p63 Deficiency: A Failure of Lineage Commitment or Stem Cell Maintenance?

A critical role for p63 in the development of stratified epithelia, such as the epidermis, has been recognized since the generation of mice lacking p63 expression. The molecular role of p63 in epidermal morphogenesis, however, remained controversial. The epidermal phenotype of p63-/- mice, which are born with a single-layered surface epithelium instead of a fully stratified epidermis, suggested that p63 could have a role in stem cell maintenance or in the commitment to stratification. In this review, we discuss evidence suggesting that p63 is required for the commitment to stratification, making p63 the earliest known gene expressed in the developing epidermis that is specific for the keratinocyte lineage.