First Author | Park KC | Year | 2017 |
Journal | J Invest Dermatol | Volume | 137 |
Issue | 2 | Pages | 414-421 |
PubMed ID | 27670610 | Mgi Jnum | J:240059 |
Mgi Id | MGI:5882275 | Doi | 10.1016/j.jid.2016.09.012 |
Citation | Park KC, et al. (2017) Skin-Specific Deletion of Mis18alpha Impedes Proliferation and Stratification of Epidermal Keratinocytes. J Invest Dermatol 137(2):414-421 |
abstractText | The Mis18 proteins (Mis18alpha, Mis18beta, and M18BP1) are pivotal to the deposition of CENP-A at the centromere during cell cycle progression and are indispensable for embryonic development. Here, we show that Mis18alpha is critical for the proliferation of keratinocytes and stratification of the epidermis. Mice lacking Mis18alpha in the epidermis died shortly after birth, showing skin abnormalities like thin and translucent skin and defective skin barrier functions. The epidermis of newborn Mis18alpha-deficient mice lacked distinct stratification and mature hair follicles, with a reduction in the number of proliferating cells and increased cell death in the basal layer. Earlier expression of the Cre recombinase from keratin-14 promoter in the ventral region resulted in earlier keratinocyte death in the ventral part compared with the dorsal part in the absence of Mis18alpha, leading to more severe malformation of the ventral epidermal layers. As observed in Mis18alpha-deficient mouse keratinocytes, knockdown of Mis18alpha in HaCaT cells caused marked loss of centromeric CENP-A dots and chromosomal misalignment. Overall, we propose that Mis18alpha is important for epidermal cell proliferation and stratification, because it is required for the deposition of CENP-A at the centromeric nucleosomes. |