Institute of Biotechnology, University of Helsinki, Finland.
Dev Dyn. 2010 Oct;239(10):2558-69. doi: 10.1002/dvdy.22395.
Nectins are immunoglobulin-like cell adhesion proteins and their interactions recruit various cell-cell junctions. Mutations in human NECTIN-1 cause an ectodermal dysplasia syndrome, but Nectin-1 null mice have only slight defects in teeth, suggesting compensation by other nectin(s). We observed overlapping expression of nectin-3 with nectin-1 and enamel abnormality in the nectin-3 mutant. We, therefore, generated nectin-1;nectin-3 compound mutants. However, all teeth developed and no significant dental abnormalities were observed before birth. At postnatal day 10, the upper molars of compound mutants exhibited conical crown shape and retarded enamel maturation. Nectin-1 was expressed in ameloblasts whereas nectin-3 was expressed in neighboring stratum intermedium cells at this stage. The immunohistochemical localization and electron microscopical observations indicated that the desmosomal junctions between stratum intermedium and ameloblasts were significantly reduced. These results suggest that heterophilic interaction between nectin-1 and nectin-3 recruits desmosomal junctions, and that these are required for proper enamel formation.
黏附蛋白家族成员是免疫球蛋白超家族细胞黏附分子，其相互作用可募集各种细胞连接。人类 NECTIN-1 基因突变可导致外胚层发育不良综合征，但 Nectin-1 敲除小鼠的牙齿仅有轻微缺陷，提示存在其他黏附蛋白（如 nectin-3）的代偿作用。我们观察到 nectin-3 与 nectin-1 具有重叠的表达模式，并且在 nectin-3 突变体中观察到釉质异常。因此，我们构建了 nectin-1;nectin-3 双基因敲除小鼠。然而，在出生前，所有牙齿均正常发育，未观察到明显的牙齿异常。出生后第 10 天，复合突变体的上颌磨牙呈现锥形冠形态，釉质成熟度延迟。在该阶段，NECTIN-1 在成釉细胞中表达，而 nectin-3 在邻近的中间层细胞中表达。免疫组织化学定位和电子显微镜观察表明，中间层和成釉细胞之间的桥粒连接明显减少。这些结果表明，nectin-1 和 nectin-3 之间的异源相互作用募集桥粒连接，这些连接对于正常釉质形成是必需的。
