Cross Talk between Cell–Cell and Cell–Matrix Adhesion Signaling Pathways during Heart Organogenesis: Implications for Cardiac Birth Defects

Abstract

The anterior-posterior and dorsal-ventral progression of heart organogenesis is well illustrated by the patterning and activity of two members of different families of cell adhesion molecules: the calcium-dependent cadherins, specifically N-cadherin, and the extracellular matrix glycoproteins, fibronectin. N-cadherin by its binding to the intracellular molecule beta-catenin and fibronectin by its binding to integrins at focal adhesion sites, are involved in regulation of gene expression by their association with the cytoskeleton and through signal transduction pathways. The ventral precardiac mesoderm cells epithelialize and become stably committed by the activation of these cell-matrix and intracellular signaling transduction pathways. Cross talk between the adhesion signaling pathways initiates the characteristic phenotypic changes associated with cardiomyocyte differentiation: electrical activity and organization of myofibrils. The development of both organ form and function occurs within a short interval thereafter. Mutations in any of the interacting molecules, or environmental insults affecting either of these signaling pathways, can result in embryonic lethality or fetuses born with severe heart defects. As an example, we have defined that exposure of the embryo temporally to lithium during an early sensitive developmental period affects a canonical Wnt pathway leading to beta-catenin stabilization. Lithium exposure results in an anterior-posterior progression of severe cardiac defects.

Kif26b , a kinesin family gene, regulates adhesion of the embryonic kidney mesenchyme

“…In addition, Smy1p, a kinesin-11 member in Saccharomyces cerevisiae, induces a conformational change in the class V myosin Myo2p, which enhances its interaction with actin and causes cell protrusion in one direction (25,26). Moreover, NMHC II-actin complexes appear to facilitate cross-talk between N-cadherin and integrins during cardiac development (27,28). Therefore, we speculate that Kif26b may enhance the interaction of NMHC II and actin, thereby stabilizing the cell-cell adhesion of mesenchymal cells and the interaction between the mesenchyme and ureteric buds through integrins in the developing kidney.…”

Cellular nonmuscle myosins NMHC‐IIA and NMHC‐IIB and vertebrate heart looping

“…Additionally, a member of a the Caϩϩ-dependent family of adhesion molecules, N-cadherin, is responsible for the connection of actin and myofibrils between neighboring myocytes at cell-cell junctions (Linask, 1992a;Kostetskii et al, 2005) and for the cell alignment and arrangement of the two layers of the developing heart tube (Shiraishi et al, 1993). Thus, during looping, as in the earlier period of cardiac compartment formation, cross-talk between two adhesion mediated-signaling pathways, integrin and N-cadherin, is evident (Linask and Lash, 1990;Linask, 1992b;Linask et al, 2005b) and as shown here, appears to be facilitated by the actinnonmuscle myosin-II complex.…”

“…This class of proteins is integral to actomyosin interactions, to cilia and involved with mechanotransduction and is a seemingly logical protein complex to be involved in heart tube bending. The well recognized intracellular cross-talk between cell-cell adhesion and cell-matrix interactions to coordinate development of form and function (Linask et al, 2005b) suggested that proteins associated with the cytoskeleton facilitate heart looping.…”

Novel embryonic stem cells expressing tdKaede protein photoconvertible from green to red fluorescence

“…In organ formation, cell fate is regulated by a combination of cell-specific genes that control intracellular events and responses to the environment, such as cell-cell and extracellular matrix-mediated interactions (4). To understand the mechanisms of differentiation through ES cells in detail, Kaede proteins may have the advantage of statically tracing the positions of living cells of interest.…”