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

ABSTRACT 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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    ABSTRACT: Aim: To study the characteristics of the location and the telomerase expression of the different developmental periods of human skin epidermal stem cells, to illuminate the significance of these characteristics to the burn wound repair. Methods: The skin samples of child and adult that came from the operation of burn and plastic, the samples of fetus came from the accidental abortion. The samples were fixed by 10% formalin at once, then were made into paraffin sections. Integrinβ1, keratin19, p63 transcription factor and telomerase reverse transcriptase (TERT) were detected by the immunohistochemistry stain. Results: The β1 integrin, K19, p63 and TERT positive cells were mainly located in the epidermal basement membrane, and the expression levels of those indexes were highest in the fetus skin, lower in the skins of the child and adult, the distribution was uniformity in the fetus and adult samples. Lowest expression in the adult sample. The expression amount of the β1 integrin, K19, p63 and TERT in the different development periods revealed decreasing with the age increasing(P<0.01). Conclusion: The epidermal stem cell of the fetus,child and adult were mainly located in the epidermal basement membrane, the positive expression sector and the expression levels of the telomerase had a same level with the location and positive expression level of the epidermal stem cells. It showed that the quantity and the expression level of the telomerase of the epidermal stem cell may have a relation with the repair ability of the different developmental periods of the skin tissue.
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    ABSTRACT: The molecular mechanisms that regulate adult neural precursor cell (NPC) survival, and thus maintain adult neurogenesis, are not well defined. Here, we investigate the role of p63, a p53 family member, in adult NPC function in mice. Conditional ablation of p63 in adult NPCs or p63 haploinsufficiency led to reduced numbers of NPCs and newborn neurons in the neurogenic zones of the hippocampus and lateral ventricles and in the olfactory bulb. These reductions were attributable to enhanced apoptosis of NPCs and newborn neurons and were rescued by inhibition of caspase activity, p53, or the p53 apoptotic effector PUMA (p53-upregulated modulator of apoptosis). Moreover, these cellular deficits were functionally important because they led to perturbations in hippocampus-dependent memory formation. These results indicate that p63 regulates the numbers of adult NPCs and adult-born neurons as well as neural stem cell-dependent cognitive functions, and that it does so, at least in part, by inhibiting p53-dependent cell death.
    Journal of Neuroscience 07/2013; 33(31):12569-85. · 6.75 Impact Factor
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    ABSTRACT: This is a chronicle of concepts in the field of epidermal stem cell biology and a historic look at their development over time. The past 25 years have seen the evolution of epidermal stem cell science, from first fundamental studies to a sophisticated science. The study of epithelial stem cell biology was aided by the ability to visualize the distribution of stem cells and their progeny through lineage analysis studies. The excellent progress we have made in understanding epidermal stem cell biology is discussed in this article. The challenges we still face in understanding epidermal stem cells include defining molecular markers for stem and progenitor sub-populations, determining the locations and contributions of the different stem cell niches, and mapping regulatory pathways of epidermal stem cell proliferation and differentiation. However, our rapidly evolving understanding of epidermal stem cells has many potential uses that promise to translate into improved patient therapy.
    Journal of Investigative Dermatology 12/2011; 132(3 Pt 2):797-810. · 6.19 Impact Factor


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