Expression of the beta 4 integrin subunit in the mouse heart during embryonic development: retinoic acid advances beta 4 expression.

Using immunohistochemical techniques as well as in situ hybridization we were able to elicit the expression pattern of the beta 4 integrin subunit in the murine heart during development. We show that beta 4 is not expressed in the heart before E13 and is afterwards restricted to the endocardium of the atrioventricular canal, the outflow tract, and the venous valves in the right atrium. As these are all sites of high shear stress in the heart, we propose a role for alpha 6 beta 4 in the tight adhesion of the endocardial cells to their basement membranes in these segments. Moreover, mouse embryos were treated with all-trans retinoic acid, which was previously shown to induce congenital malformations, among which malformations of the heart. We show an advanced expression without ectopic localization of cardiac beta 4 after the administration of retinoic acid. This advanced appearance of beta 4 was also shown in extracardiac tissue like migrating neural crest cells. Several hypotheses on the mechanism of beta 4 up-regulation and a possible role for alpha 6 beta 4 in the development of heart malformations after the administration of retinoic acid are discussed.