Dataset Information

Disruption of epidermal specific gene expression and delayed skin development in AP-2 gamma mutant mice.

ABSTRACT: Summary Sentence: Conditional ablation of AP-2 gamma results in a delay in skin development and abnormal expression of p63, K14, K1, filaggrin, repetin and secreted Ly6/Plaur domain containing 1, key genes required for epidermal development and differentiation. The development of the epidermis, a stratified squamous epithelium, is dependent on the regulated differentiation of keratinocytes. Differentiation begins with the initiation of stratification, a process tightly controlled through proper gene expression. AP-2 gamma is expressed in skin and previous research suggested a pathway where p63 gene induction results in increased expression of AP-2 gamma, which in turn is responsible for induction of K14. This study uses a conditional gene ablation model to further explore the role of AP-2 gamma in skin development. Mice deficient for AP-2 gamma exhibited delayed expression of p63, K14, and K1, key genes required for development and differentiation of the epidermis. In addition, microarray analysis of E16.5 skin revealed delayed expression of additional late epidermal differentiation genes: filaggrin, repetin and secreted Ly6/Plaur domain containing 1, in mutant mice. The genetic delay in skin development was further confirmed by a functional delay in the formation of an epidermal barrier. These results document an important role for AP-2 gamma in skin development, and reveal the existence of regulatory factors that can compensate for AP-2 gamma in its absence.

SUBMITTER: Guttormsen J

PROVIDER: S-EPMC2435508 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Disruption of epidermal specific gene expression and delayed skin development in AP-2 gamma mutant mice.

Guttormsen Jillian J Koster Maranke I MI Stevens John R JR Roop Dennis R DR Williams Trevor T Winger Quinton A QA

Developmental biology 20080221 1

Summary Sentence: Conditional ablation of AP-2 gamma results in a delay in skin development and abnormal expression of p63, K14, K1, filaggrin, repetin and secreted Ly6/Plaur domain containing 1, key genes required for epidermal development and differentiation. The development of the epidermis, a stratified squamous epithelium, is dependent on the regulated differentiation of keratinocytes. Differentiation begins with the initiation of stratification, a process tightly controlled through proper ...[more]

PMID: 18353300

Similar Datasets

Project description:Endogenous and synthetic glucocorticoids (GCs) regulate epidermal development and combat skin inflammatory diseases. GC actions can be mediated through the GC receptor (GR) and/or the mineralocorticoid receptor (MR), highly homologous ligand-activated transcription factors. While the role of GR as a potent anti-inflammatory mediator is well known, that of MR is not as clear, nor is whether these receptors cooperate or antagonize each other in the epidermis. To address this, we generated mice with epidermal-specific loss of both receptors (double knockout, DKO), and analyzed the phenotypical and functional consequences relative to single KOs or controls (CO). At birth, DKO epidermis displayed a phenotype of defective differentiation and inflammation, which was more severe than in either single KO, featuring neutrophil-containing infiltrates, and gene dysregulation characteristic of human psoriatic lesions. This phenotype resolved spontaneously. However, in adulthood, single or combined loss of GC receptors increased susceptibility to inflammation and hyperproliferation triggered by phorbol ester which, different to CO, was not effectively counteracted by GC treatment. Also, DKOs were more susceptible to imiquimod-induced psoriasis than CO showing severe defective epidermal differentiation and microabcesses while single KOs showed an intermediate response. Immortalized DKO keratinocytes featured increased proliferation kinetics and reduced cell size, a unique phenotype relative to single KO cells. The lack of GR and MR in keratinocytes, individual or combined, caused constitutive increases in p38 and ERK activities, which were partially reversed upon reinsertion of receptors into DKO cells. DKO keratinocytes also displayed significant increases in AP-1 and NF-?B transcriptional activities, which were partially rescued by ERK and p38 inhibition, respectively. Reinsertion of GR and MR in DKO keratinocytes resulted in physical and cooperative functional interactions that restored the transcriptional response to GCs. In conclusion, our data have revealed that epidermal GR and MR act cooperatively to regulate epidermal development and counteract skin inflammation.

Dataset Information

Disruption of epidermal specific gene expression and delayed skin development in AP-2 gamma mutant mice.

Publications

Disruption of epidermal specific gene expression and delayed skin development in AP-2 gamma mutant mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets