Terminal differentiation of nail matrix keratinocytes involves up-regulation of DNase1L2 but is independent of caspase-14 expression

Abstract Terminal differentiation of keratinocytes in the epidermis and in epidermal appendages results in specialized forms of cell death. Keratinocytes of the nail matrix differentiate into nail corneocytes, the building blocks of the nail plate. Here, we show that, in contrast to the abrupt breakdown of the nucleus during corneocyte formation of epidermal keratinocytes, chromatin undergoes progressive condensation over several nail matrix cell layers below the transition zone to the nail plate, where nuclear DNA disappears. Virtually all keratinocytes in the cell layer immediately beneath the nail plate contained terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling-positive DNA fragments. Nail matrix keratinocytes lacked processed caspase-3, a marker of apoptosis, and did not express caspase-14, a protease up-regulated during terminal differentiation of epidermal keratinocytes. By contrast, DNase1L2, which is also up-regulated during the differentiation of epidermal keratinocytes and plays an essential role in differentiation-associated degradation of nuclear DNA in epidermal keratinocytes, was strongly expressed in the nail matrix–nail plate transition layer. Our results show that caspase-14 is not strictly, if at all, required for differentiation-associated keratinocyte cell death and implicates DNase1L2 in terminal differentiation of nail matrix keratinocytes.