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

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Journal of Investigative Dermatology Symposium Proceedings (Impact Factor: 3.73). 12/2005; 10(2):118-23. DOI: 10.1111/j.1087-0024.2005.200416.x
Source: PubMed


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.

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    • "One protein that is critical for transit amplifying cell regulation is p63. It has been suggested that ΔNp63 is involved in maintaining transit amplifying cells and in preventing premature onset of differentiation (Truong et al, 2006; Honeycutt et al, 2004; Koster et al, 2005) and ΔNp63 was found to be important for maintaining the proliferative state of transit amplifying cells (Truong et al, 2006). p63 is strongly expressed in epithelial cells with high clonogenic and proliferative capacity (Senoo et al, 2007) and mice with reduced ΔNp63 expression show excessive keratinocyte proliferation while lacking normal differentiated layers (Koster et al, 2007). "
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    • "downregulated in more differentiated layers (Koster et al, 2004). Importantly, DNp63 maintains the stem cell population in the proliferative compartment of stratified epithelia (Mills et al, 1999; Yang et al, 1999; Pellegrini et al, 2001; Koster et al, 2005). Recent studies through conditional gene deletion show that p63 also regulates the proliferative potential of epidermal stem cells in adult skin and subsequently influences cell senescence and ageing in mice (Keyes et al, 2005; Senoo et al, 2007; Guo et al, 2009). "
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