Understanding and Harnessing Epithelial‒Mesenchymal Interactions in the Development of Palmoplantar Identity

Abstract

Palmoplantar skin has several unique characteristics such as increased thickness, high resilience, hypopigmentation, and lack of hair follicles. The establishment of palmoplantar identity occurs through keratinocyte‒fibroblast interactions, with keratin 9 expression and Wnt signaling playing key roles. Understanding how palmoplantar features develop may help efforts to reproduce them at both palmoplantar and nonpalmoplantar body sites.

Trial registration: ClinicalTrials.gov NCT03947450.

Figure 1.. Signaling molecules and pathways likely involved in the development of palmoplantar characteristics.

Expression of keratin 9 (KRT9) is a marker for palmoplantar keratinocyte differentiation, but there is uncertainty on whether KRT9 expression results from activation or inhibition of canonical Wnt signaling. Additional molecules including Dickkopf (DKK) proteins, R-spondin (RSPO) proteins, double-stranded RNA (dsRNA), inactive rhomboid protein 2 (iRHOM2), and epidermal growth factor (EGF) have been implicated in regulation of Wnt signaling or KRT9 expression, warranting further study on the interaction of different signaling pathways in the context of palmoplantar biology.