Brdm2—an aberrant hypomorphic p63 allele

Talos, Flaminia; Wolff, Sonja; Beyer, Ulrike; Dobbelstein, Matthias; Moll, Ute M.

doi:10.1038/cdd.2009.158

Cited by 8 publications

(6 citation statements)

References 10 publications

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“…[32][33][34] In any case, given our results, a putative pro-apoptotic function of p63 in sympathetic neurons can clearly not be generalized to neurons and glia of the developing CNS.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

While p73 is essential, p63 is completely dispensable for the development of the central nervous system

Holembowski¹,

Schulz²,

Talos³

et al. 2011

Cell Cycle

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“…[32][33][34] In any case, given our results, a putative pro-apoptotic function of p63 in sympathetic neurons can clearly not be generalized to neurons and glia of the developing CNS.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

While p73 is essential, p63 is completely dispensable for the development of the central nervous system

Holembowski¹,

Schulz²,

Talos³

et al. 2011

Cell Cycle

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“…25 It has an antiproliferative role, fundamental for skin development and differentiation, targeting the 3′-UTR of the transcription factor p63. 22, 26 Indeed, p63, a member of the p53 family, has an important role in maintaining basal keratinocyte proliferative potential in adult normal epidermis, 27, 28, 29, 30, 31, 32, 33 during development 34, 35, 36, 37 and in pathological conditions. 23, 24, 38, 39 MiR-203 downregulation, as described in several cancers, 42, 43, 44, 45, 46 promotes EMT transition and enables tumor cells to acquire invasive metastatic features.…”

mentioning

confidence: 99%

MicroRNA-203 contributes to skin re-epithelialization

et al. 2012

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Keratinocyte proliferation and migration are crucial steps for the rapid closure of the epidermis during wound healing, but the molecular mechanisms involved in this cellular response remain to be completely elucidated. Here, by in situ hybridization we characterize the expression pattern of miR-203 after the induction of wound in mouse epidermis, showing that its expression is downregulated in the highly proliferating keratinocytes of the ‘migrating tongue', whereas it is strongly expressed in the differentiating cells of the skin outside the wound. Furthermore, subcutaneous injections of antagomiR-203 in new born mice dorsal skin strengthened, in vivo, the inverse correlation between miR-203 expression and two new target mRNAs: RAN and RAPH1. Our data suggest that miR-203, by controlling the expression of target proteins that are responsible for both keratinocyte proliferation and migration, exerts a specific role in wound re-epithelialization and epidermal homeostasis re-establishment of injured skin.

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“…Given this altered keratin profile and the failure to detect any markers of keratinocyte differentiation, the p63-null phenotype was attributed to a block in lineage commitment of the ectodermal cells to an epidermal fate (Koster et al, 2004;Mills et al, 1999). Recent reports that the mouse model developed by the Bradley laboratory might represent a hypomorphic allele of p63 have sparked additional debate about the shortcomings of the existing genetic models (Mikkola et al, 2010;Talos et al, 2010;Wolff et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

ΔNp63 knockout mice reveal its indispensable role as a master regulator of epithelial development and differentiation

et al. 2012

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SUMMARYThe transcription factor p63 is important in the development of the skin as p63-null mice exhibit striking defects in embryonic epidermal morphogenesis. Understanding the mechanisms that underlie this phenotype is complicated by the existence of multiple p63 isoforms, including TAp63 and DNp63. To investigate the role of DNp63 in epidermal morphogenesis we generated DNp63 knock-in mice in which the DNp63-specific exon is replaced by GFP. Homozygous DNp63 gfp/gfp animals exhibit severe developmental anomalies including truncated forelimbs and the absence of hind limbs, largely phenocopying existing knockouts in which all p63 isoforms are deleted. DNp63-null animals show a poorly developed stratified epidermis comprising isolated clusters of disorganized epithelial cells. Despite the failure to develop a mature stratified epidermis, the patches of DNp63-null keratinocytes are able to stratify and undergo a program of terminal differentiation. However, we observe premature expression of markers associated with terminal differentiation, which is unique to DNp63-null animals and not evident in the skin of mice lacking all p63 isoforms. We posit that the dysregulated and accelerated keratinocyte differentiation phenotype is driven by significant alterations in the expression of key components of the Notch signaling pathway, some of which are direct transcriptional targets of DNp63 as demonstrated by ChIP experiments. The analysis of DNp63 gfp/gfp knockout mice reaffirms the indispensable role of the DN isoform of p63 in epithelial biology and confirms that DNp63-null keratinocytes are capable of committing to an epidermal cell lineage, but are likely to suffer from diminished renewal capacity and an altered differentiation fate.

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Brdm2—an aberrant hypomorphic p63 allele

Cited by 8 publications

References 10 publications

While p73 is essential, p63 is completely dispensable for the development of the central nervous system

While p73 is essential, p63 is completely dispensable for the development of the central nervous system

MicroRNA-203 contributes to skin re-epithelialization

ΔNp63 knockout mice reveal its indispensable role as a master regulator of epithelial development and differentiation

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