Cooperation of nectin‐1 and nectin‐3 is required for normal ameloblast function and crown shape development in mouse teeth

Abstract

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. Developmental Dynamics 239:2558-2569,

Tooth Organ Engineering: Biological Constraints Specifying Experimental Approaches

“…2A, C ;Hu et al, 2005). This stratum intermedium plays an essential role in the functional differentiation of ameloblasts (Lesot & Brook, 2009;Nait Lechguer et al, 2011;Yoshida et al, 2010). Only in one report, non polarized ameloblasts-like cells expressing amelogenin appeared to be generated in the absence of a stratum intermedium (Honda & Hata, 2010).…”

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

“…Hence, nectin-1 null mutant mice do not recapitulate the phenotypes of human CLPED1 and they cannot be used as an appropriate animal model to examine the pathogenesis of CLPED1 or the role of nectins in the morphogenesis of ectodermal organs. As previous studies have reported that overlapping expression of nectins in skin and nectins may act via heterophilic nectin-nectin interactions, we hypothesized that the function of nectin-1 may be compensated by other nectins in mice [8,24]. As the interaction between nectin-1 and nectin-3 is the strongest among nectin interactions [2] and nectin-1 and nectin-3 mutant mice have overlapping abnormalities, nectin-3 appeared as a good candidate for the compensating nectin.…”

“…Recent studies in mouse show that nectin interactions are involved in formation and/or maintenance of desmosomes as well [7,8]. The identification of mutations in NECTIN-1 (PVRL1) gene as the cause of severe human ectodermal dysplasia (ED) syndrome Cleft Lip/Palate-Ectodermal Dysplasia Syndrome 1 (CLPED1, MIM 225060) indicates an important role for nectin in the development of mammalian skin and its appendages [9,10].…”

“…During mouse development, nectins are expressed in ectodermal tissues including epidermis and hair follicle [8,23,24]. Nectin-1, nectin-2, and nectin-3 have been knocked out in mice, but none of the single mutant mouse lines exhibits severe abnormalities in ectodermal organs.…”

“…Neither epidermis nor hair abnormalities have been reported in nectin-2 null mutants [25,26]. Nectin-3 null mutants exhibit mild defects in dental enamel, eye, and neurogenesis [8,[27][28][29]. Intriguingly, although CLPED1 patients exhibiting mutations in NECTIN-1 gene manifest severe aberrations in hair and tooth development, nectin-1 deficient mice have only mild defects in skin including fragile epidermis with reduced expression of the granular layer marker loricrin, and minor defects in enamel [7,8,30].…”