title: Aurora kinase-A deficiency during skin development impairs cell division and stratification.
abstract: 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.
authors: Department of Dermatology, University of Colorado, Denver, CO, USA.
authors: Enrique C
authors: EC
authors: Torchia
authors: Lei
authors: L
authors: Zhang
authors: Aaron J
authors: AJ
authors: Huebner
authors: Subrata
authors: S
authors: Sen
authors: Dennis R
authors: DR
authors: Roop
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D064096:Aurora Kinase A; D064127:Aurora Kinases; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D018385:Centrosome / Q000201:enzymology; D017353:Gene Deletion; D053556:Keratin-1; D053547:Keratin-14 / Q000096:biosynthesis; D015603:Keratinocytes / Q000502:physiology; D053564:Keratins, Hair-Specific / Q000096:biosynthesis; D051379:Mice; D011123:Polyploidy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D012867:Skin / Q000201:enzymology* / Q000254:growth & development* / Q000473:pathology; D013234:Stem Cells / Q000502:physiology
chemical_list: D053556:Keratin-1; D053547:Keratin-14; D053564:Keratins, Hair-Specific; C507530:Krt1 protein, mouse; C507446:Krt14 protein, mouse; C576918:Aurka protein, mouse; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases