Transient elevation of cytoplasmic calcium ion concentration at a single cell level precedes morphological changes of epidermal keratinocytes during cornification

Epidermal keratinocytes achieve sequential differentiation from basal to granular layers, and undergo a specific programmed cell death, cornification, to form an indispensable barrier of the body. Although elevation of the cytoplasmic calcium ion concentration ([Ca2+](i)) is one of the factors predicted to regulate cornification, the dynamics of [Ca2+](i) in epidermal keratinocytes is largely unknown. Here using intravital imaging, we captured the dynamics of [Ca2+](i) in mouse skin. [Ca2+](i) was elevated in basal cells on the second time scale in three spatiotemporally distinct patterns. The transient elevation of [Ca2+](i) also occurred at the most apical granular layer at a single cell level, and lasted for approximately 40 min. The transient elevation of [Ca2+](i) at the granular layer was followed by cornification, which was completed within 10 min. This study demonstrates the tightly regulated elevation of [Ca2+](i) preceding the cornification of epidermal keratinocytes, providing possible clues to the mechanisms of cornification.