Atypical E-cadherin attachments mediate melanoblast migration through confined epithelial spaces

Epithelial tissues are populated with accessory cells including pigment-producing melanocytes, which must migrate between tightly adherent epithelial cells, but how cells migrate through confined epithelial spaces without impairing barrier function is poorly understood. Using live imaging of the mouse epidermis, we captured the migration of embryonic melanocytes (melanoblasts) while simultaneously visualizing the basement membrane or epithelial surfaces. We show that melanoblasts migrate through basal and suprabasal layers of the epidermis where they use keratinocyte surfaces, as well as the basement membrane, as substrates for migration. Melanoblasts form atypical and dynamic E-cadherin attachments to keratinocytes that largely lack cytoplasmic catenins known to anchor E-cadherin to F-actin. We show E-cadherin is needed in both melanoblasts and keratinocytes to stabilize migratory protrusions, and that depleting E-cadherin results in reduced melanoblast motility and ventral depigmentation in adult mice. These findings illustrate how migratory cells modify the cell adhesion machinery to invade between connected epithelial cells without interrupting the skin barrier.