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

被引:22
作者
Guttormsen, Jillian [1 ]
Koster, Maranke I. [6 ,7 ,8 ,9 ]
Stevens, John R. [1 ]
Roop, Dennis R. [6 ,7 ,8 ,9 ]
Williams, Trevor [2 ,3 ,4 ,5 ]
Winger, Quinton A. [1 ]
机构
[1] Utah State Univ, Dept Anim Dairy & Vet Sci, Logan, UT 84322 USA
[2] Univ Colorado, Dept Craniofacial Biol, Aurora, CO USA
[3] Univ Colorado, Dept Cell & Dev Biol, Aurora, CO USA
[4] Univ Colorado, Dept Cell & Dev Biol, Denver, CO 80202 USA
[5] Univ Colorado, Dept Craniofacial Biol, Denver, CO 80202 USA
[6] Univ Colorado, Dept Dermatol, Aurora, CO USA
[7] Univ Colorado, Charles C Gates Regenerat Med & Stem Cell Biol Pr, Aurora, CO USA
[8] Univ Colorado, Charles C Gates Regenerat Med & Stem Cell Biol Pr, Denver, CO 80202 USA
[9] Univ Colorado, Dept Dermatol, Denver, CO 80202 USA
关键词
AP-2; Tefap2c; skin; epidermis; keratinocyte; filaggrin; keratin; differentiation; embryo development;
D O I
10.1016/j.ydbio.2008.02.017
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Conditional ablation of AP-2-gamma results in a delay in skin development and abnormal expression of p63, K 14, K 1, 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. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:187 / 195
页数:9
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