Under Pressure: A unique mechanoresponsive mechanism of body site-specific keratin regulation in palmoplantar epidermis

However, the mechanisms specifying and maintaining its distinct identity remain incompletely defined. Here, we identify the type 1 keratin 9 (KRT9/K9), a protein uniquely expressed in the palmoplantar epidermis, as a key modulator of mechanosensitive YAP1 signaling in response to postnatal mechanical compression.

K9 loss-of-function variants, as observed in human KRT9 palmoplantar epidermal differentiation disorder (KRT9-pEDD), results in aberrant YAP1 subcellular partitioning and elevated levels of the stress-induced keratin 16 (KRT16/K16). Krt9 null mice recapitulate these molecular phenotypes as early as postnatal day 3 (P3). We further identify dynamic, YAP1-dependent regulation of Krt9/K9 and Krt16/K16 during early postnatal development and in response to ex vivo mechanical compression, highlighting the role of mechanical stress in epidermal specification.