Mucosal addressin cell adhesion molecule 1 plays an unexpected role in the development of mouse guard hair.

The first wave of coat hair development is initiated around embryonic day 14 in the mouse. Whereas ectodysplasin and ectodermal dysplasia receptor, tumor necrosis factor and tumor necrosis factor receptor family molecules, respectively, were identified to be signals triggering this process, not much was known regarding their downstream molecular targets. In this report, we show that mucosal addressin cell adhesion molecule 1 and intercellular adhesion molecule 1 are induced in the keratinocytes of the hair placode as a direct consequence of ectodermal dysplasia receptor signal, and tumor-necrosis-factor-receptor-associated factor 6 is involved in this mucosal addressin cell adhesion molecule 1 expression. Experiments using an in vitro culture of skin fragments demonstrated that ectodermal-dysplasia-receptor-induced mucosal addressin cell adhesion molecule 1 expression occurs at the initial phase of follicle development before involvement of Sonic hedgehog signal. Follicle development in this culture was also suppressed to some extent, though not completely, by addition of soluble mucosal addressin cell adhesion molecule 1/IgG-Fc chimeric protein, whereas monoclonal antibody that can inhibit mucosal addressin cell adhesion molecule 1 interaction with integrin alpha4beta7 had no effect on this process. These results demonstrated for the first time that the structural proteins, mucosal addressin cell adhesion molecule 1 and intercellular adhesion molecule 1, are induced by ectodermal dysplasia receptor signal and suggested the potential involvement of mucosal addressin cell adhesion molecule 1 in the morphogenesis of follicular keratinocytes.