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Aurora kinase-A deficiency during skin development impairs cell division and stratification.
Torchia, Enrique C; Zhang, Lei; Huebner, Aaron J; Sen, Subrata; Roop, Dennis R.
Afiliação
  • Torchia EC; Department of Dermatology, University of Colorado, Denver, CO, USA.
J Invest Dermatol ; 133(1): 78-86, 2013 Jan.
Article em En | MEDLINE | ID: mdl-22832491
Aurora kinase-A (Aurora-A) promotes timely entry into mitosis, centrosome maturation, and formation of bipolar spindles. To address the role of Aurora-A in skin development and homeostasis, we interbred a floxed Aurora-A (Aurora-A(fl)) mouse with the Cre-deleter strain, K14.Cre. Aurora-A(fl/fl);Krt14.Cre (Aurora-A(-/-)) mice died shortly after birth. These mice had translucent skin, and histological evaluation showed that the dorsal skin was very thin and fragile with frank erosions. Although the expression of the basal layer marker keratin 14 and the differentiation marker keratin 1 was evident in Aurora-A(-/-) epidermis, there was a marked reduction in the number of suprabasal layers and basal keratinocytes. Dye exclusion assays also showed defects in barrier function. Unlike wild-type cells, Aurora-A(-/-) basal progenitors were delayed in forming two layers at embryonic day (E)13.5 when embryonic skin begins to stratify. Increased numbers of mitotic cells, apoptotic bodies, and polyploid keratinocytes were evident in Aurora-A(-/-) epidermis, indicating that a deficiency in Aurora-A promotes aberrant mitosis, mitotic slippage, and cell death. Finally, Aurora-A(-/-) keratinocytes displayed centrosomal abnormalities that included centrosomes located at nonapical sites in basal cells. Thus, the deletion of Aurora-A in the developing epidermis alters centrosome function of basal keratinocytes and markedly impairs their ability to divide and stratify.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pele / Divisão Celular / Proteínas Serina-Treonina Quinases Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Invest Dermatol Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pele / Divisão Celular / Proteínas Serina-Treonina Quinases Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Invest Dermatol Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Estados Unidos