Abstract
Nectins constitute a family of four cell adhesion molecules which are localized on cell membrane. Mutations in NECTIN-1 gene cause the human ectodermal dysplasia syndrome (CLPED1) manifesting severe defects in skin and its appendages. However, nectin-1 null mutant mice have only a mild defect in epidermal stratification suggesting compensation by other nectins. We have analysed the epidermal and hair phenotypes of nectin-1; nectin-3 compound mutants. Epidermis was fragile and displayed severe defects in stratification, hair follicles were hypoplastic, and hair shaft structure was abnormal. Immunohistochemical analysis revealed severe defects in cell-cell junctions including adherens and tight junctions as well as desmosomes. It is therefore likely that the phenotypes were caused by impaired cell adhesion. The expression patterns of nectin-1 and nectin-3 together with the phenotypes in compound mutants indicated that heterophilic interactions between the two nectins are required for proper formation of epidermis and hair in mice. The nectin-1; nectin-3 compound mutant mice partially reproduced the phenotype of human CLPED1 patients.
Highlights
Nectins are immunoglobulin- (Ig-) like, calcium-independent cell adhesion molecules involved in various cellular and physiological processes including proliferation, migration, polarization, and adhesion [1]
Since the expression of nectin-3 could not be detected by immunohistochemistry, we used radioactive in situ hybridization (ISH)
Previous studies have reported that nectin-1 is expressed in the suprabasal layer of epidermis and in all cells of the whisker follicle except for outer root sheath (ORS) [23, 24, 30], while no obvious expression of nectin-3 was observed in these tissues [24]
Summary
Nectins are immunoglobulin- (Ig-) like, calcium-independent cell adhesion molecules involved in various cellular and physiological processes including proliferation, migration, polarization, and adhesion [1]. Previous studies demonstrated that mutant mice exhibiting modulation of cell adhesion and loss of junctional proteins show abnormal differentiation and structure of both epidermis and hair follicles [22] These reports indicate the importance of cell-cell junctions for skin development and homeostasis. 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]. The expressions and localization of cell adhesion molecules associated with adherens and tight junctions and desmosomes were severely impaired in the compound mutant epidermis and hair follicles These abnormalities were not observed during embryonic development. Our results indicated that cooperation of nectin-1 and nectin-3 is important for postnatal development and homeostasis of mouse epidermis and pelage hair
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