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 β-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
β-catenin stabilization. Lithium exposure results in an
anterior–posterior progression of severe cardiac defects.
