Cooperation of Nectin-1 and Nectin-3 Is Required for Maintenance of Epidermal Stratification and Proper Hair Shaft Formation in the Mouse

Figure 3

Defects in cell differentiation and cell-cell junctions in compound mutant epidermis. Immunohistochemical analysis of dorsal epidermis of control ((a)–(d), (i)–(k), and (o)), nectin-1−/−; nectin-3+/− ((e)–(h), (l)–(n), and (p)), and nectin-1+/−; nectin-3−/− (p) at P10. The continuous expression of laminin in the basement membrane of the control skin (arrowhead in (a)) is mostly lost in the nectin-1−/−; nectin-3+/−, with only little remaining expression (arrowheads in (e)). K14 expression in the basal layer is weaker and the structure is disorganized in the nectin-1−/−; nectin-3+/− ((b) and (f)). Arrowheads in (b) and (f) indicate the region magnified in inset. K10 expression is observed in the spinous layer both in the control (c) and the nectin-1−/−; nectin-3+/− (g). Loricrin and filaggrin are severely reduced in the nectin-1−/−; nectin-3+/− compared with the control ((d), (i), (h), and (l)). Ki67 and p63 are completely lost from the basal layer cells in the nectin-1−/−; nectin-3+/− ((j), (k), (m), and (n)). ((o) and (p)) Triple staining with antibodies against p63 and K14 and with DAPI for the nuclei. Arrowheads indicate the same cell in different staining. In nectin-1+/−; nectin-3−/− mutant epidermis, the cells that are negative for p63 exhibit disrupted or no expression of K14 (arrowheads in (p)). Dashed lines: basement membrane. Scale bars are 30 μm in (a)–(i), (l), (o), and (p) and 10 μm in (j), (k), (m), and (n).