%0 Journal Article
%T Cooperation of Nectin-1 and Nectin-3 Is Required for Maintenance of Epidermal Stratification and Proper Hair Shaft Formation in the Mouse
%A Toshiyuki Yoshida
%A Yoshimi Takai
%A Irma Thesleff
%J Developmental Biology Journal
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/432043
%X 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. 1. Introduction Nectins are immunoglobulin- (Ig-) like, calcium-independent cell adhesion molecules involved in various cellular and physiological processes including proliferation, migration, polarization, and adhesion [1]. The nectins are encoded by PVRL genes and the family is composed of four members, nectin-1 to nectin-4. Each nectin has an N-terminal extracellular domain with three Ig loops, a transmembrane domain, and a C-terminal intracellular domain. Nectins interact with nectins or other cell surface molecules on adjacent cells through the Ig loops. The nectin-nectin interactions are either homophilic or heterophilic, that is, interactions between the same or a different nectin, respectively [2]. The nectin interaction elicits intracellular signalling via the binding of the C-terminal domain to afadin [3]. Of the cellular functions regulated by nectins, cell adhesion has been extensively studied. Nectin signalling recruits cadherins to the junctional site forming an adherens junction, and this is followed by the recruitment of claudins forming a tight junction [4¨C6]. 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
%U http://www.hindawi.com/journals/dbj/2014/432043/