p63 in Skin Development and Ectodermal Dysplasias

Koster, Maranke I.

doi:10.1038/jid.2010.119

Cited by 81 publications

(74 citation statements)

References 76 publications

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“…The p53 homolog p63 is one of the earliest transcription factors expressed during epidermal specification (Koster and Roop, 2007) and is associated with ectodermal appendage specification, epidermal cell proliferation and development (Koster, 2010;Laurikkala et al, 2006;Lechler and Fuchs, 2005;Mills et al, 1999;Truong and Khavari, 2007;Yang et al, 1999). Alternative splicing of the p63 gene yields transcripts encoding two classes of p63 protein isoforms, TAp63 and ΔNp63.…”

Section: Introductionmentioning

confidence: 99%

Notch signaling represses p63 expression in the developing surface ectoderm

Tadeu

Horsley

2013

Development

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MiceK14-H2BGFP transgenic mice (Tumbar et al., 2004) SUMMARYThe development of the mature epidermis requires a coordinated sequence of signaling events and transcriptional changes to specify surface ectodermal progenitor cells to the keratinocyte lineage. The initial events that specify epidermal keratinocytes from ectodermal progenitor cells are not well understood. Here, we use both developing mouse embryos and human embryonic stem cells (hESCs) to explore the mechanisms that direct keratinocyte fate from ectodermal progenitor cells. We show that both hESCs and murine embryos express p63 before keratin 14. Furthermore, we find that Notch signaling is activated before p63 expression in ectodermal progenitor cells. Inhibition of Notch signaling pharmacologically or genetically reveals a negative regulatory role for Notch signaling in p63 expression during ectodermal specification in hESCs or mouse embryos, respectively. Taken together, these data reveal a role for Notch signaling in the molecular control of ectodermal progenitor cell specification to the epidermal keratinocyte lineage.

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Section: Introductionmentioning

confidence: 99%

Notch signaling represses p63 expression in the developing surface ectoderm

Tadeu

Horsley

2013

Development

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“…30 Consistent with the role of p63 in epidermal commitment of ectodermal progenitors, heterozygous germline mutations in TP63 result in human ED syndromes involving defective development of the limbs, and/or ED characterized by defects in skin and its associated structures. 31 Several recent reviews have focused upon the function of DNp63 in embryogenesis and in the adult, [32][33][34] as well as in cancer. 4 Here, we review two new functions recently attributed to TAp63 in premature aging of the skin 35 and during cardiac development 36 and discuss their potential implications to human pathologies.…”

Section: Function and Regulation Of Dnp63 In Epithelial Developmentmentioning

confidence: 99%

Regulation of skin aging and heart development by TAp63

et al. 2011

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Since the discovery of the TP63 gene in 1998, many studies have demonstrated that DNp63, a p63 isoform of the p53 gene family, is involved in multiple functions during skin development and in adult stem/progenitor cell regulation. In contrast, TAp63 studies have been mostly restricted to its apoptotic function and more recently as the guardian of oocyte integrity. TAp63 endogenous expression is barely detectable in embryos and adult (except in oocytes), presumably because of its rapid degradation and the lack of antibodies able to detect weak expression. Nevertheless, two recent independent studies have demonstrated novel functions for TAp63 that could have potential implications to human pathologies. The first discovery is related to the protective role of TAp63 on premature aging. TAp63 controls skin homeostasis by maintaining dermal and epidermal progenitor/stem cell pool and protecting them from senescence, DNA damage and genomic instability. The second study is related to the role of TAp63, expressed by the primitive endoderm, on heart development. This unexpected role for TAp63 has been discovered by manipulation of embryonic stem cells in vitro and confirmed by the severe cardiomyopathy observed in brdm2 p63-null embryonic hearts. Interestingly, in both cases, TAp63 acts in a cell-nonautonomous manner on adjacent cells. Here, we discuss these findings and their potential connection during development.

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“…Numerous other critical developmental pathways affect epithelium and are associated with enamel defects. For example, the WNT10A, TP63, PORCN, and DLX3 genes are all associated with syndromes that have abnormal ectodermal appendage development and can have defective enamel formation (Price et al 1998;Adaimy et al 2007;Wang et al 2007;Koster 2010). Given that the genes and gene products can be interactive (PORCN and WNT,TP63 and DLX3), it is not surprising that similar developmental defects and phenotypes might occur.…”

Section: Discussionmentioning

confidence: 99%

The Molecular Basis of Hereditary Enamel Defects in Humans

2014

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The formation of human enamel is highly regulated at the molecular level and involves thousands of genes. Requisites for development of this highly mineralized tissue include cell differentiation; production of a unique extracellular matrix; processing of the extracellular matrix; altering of cell function during different stages of enamel formation; cell movement and attachment; regulation of ion and protein movement; and regulation of hydration, pH, and other conditions of the microenvironment, to name just a few. Not surprising, there is a plethora of hereditary conditions with an enamel phenotype. The objective of this review was to identify the hereditary conditions listed on Online Mendelian Inheritance in Man (OMIM) that have an associated enamel phenotype and whether a causative gene has been identified. The OMIM database was searched with the terms amelogenesis, enamel, dental, and tooth, and all results were screened by 2 individuals to determine if an enamel phenotype was identified. Gene and gene product function was reviewed on OMIM and from publications identified in PubMed. The search strategy revealed 91 conditions listed in OMIM as having an enamel phenotype, and of those, 71 have a known molecular etiology or linked genetic loci. The purported protein function of those conditions with a known genetic basis included enzymes, regulatory proteins, extracellular matrix proteins, transcription factors, and transmembrane proteins. The most common enamel phenotype was a deficient amount of enamel, or enamel hypoplasia, with hypomineralization defects being reported less frequently. Knowing these molecular defects allows an initial cataloging of molecular pathways that lead to hereditary enamel defects in humans. This knowledge provides insight into the diverse molecular pathways involved in enamel formation and can be useful when searching for the genetic etiology of hereditary conditions that involve enamel.

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p63 in Skin Development and Ectodermal Dysplasias

Cited by 81 publications

References 76 publications

Notch signaling represses p63 expression in the developing surface ectoderm

Notch signaling represses p63 expression in the developing surface ectoderm

Regulation of skin aging and heart development by TAp63

The Molecular Basis of Hereditary Enamel Defects in Humans

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