Expression of the β4 integrin subunit in the mouse heart during embryonic development: Retinoic acid advances β4 expression

Abstract

Using immunohistochemical techniques as well as in situ hybridization we were able to elicit the expression pattern of the β4 integrin subunit in the murine heart during development. We show that β4 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 α6β4 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 realformations of the heart. We show an advanced expression without ectopic localization of cardiac β4 after the administration of retinoic acid. This advanced appearance of β4 was also shown in extracardiac tissue like migrating neural crest cells. Several hypotheses on the mechanism of β4 upregulation and a possible role for α6β4 in the development of heart realformations after the administration of retinoic acid are discussed.