TY - JOUR
T1 - Aurora kinase-a deficiency during skin development impairs cell division and stratification
AU - Torchia, Enrique C.
AU - Zhang, Lei
AU - Huebner, Aaron J.
AU - Sen, Subrata
AU - Roop, Dennis R.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health: R01CA52607 (DRR) and RO1CA89716 (SS). We thank Leila Garcia and the University of Colorado Cancer Center Cytogenetics Core for performing the FISH experiments (P30 CA046934), David Sheneman for technical assistance, and Miss Irene Choi for her assistance in the preparation of the manuscript. We also acknowledge support from the University of Colorado Skin Disease Research Center Morphology and Phenotyping Core facility (P30 AR057212).
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
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U2 - 10.1038/jid.2012.249
DO - 10.1038/jid.2012.249
M3 - Article
C2 - 22832491
AN - SCOPUS:84872180569
SN - 0022-202X
VL - 133
SP - 78
EP - 86
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 1
ER -