Chapter 6.2 – Signaling Pathways in Valve Formation: The Origin of Congenital Defects

Publisher Summary This chapter focuses on cardiac valve formation and the molecular signals that regulate this process. It also analyzes the molecular and cellular properties of the embryonic endocardium, as well as the specific molecular crosstalk between the endocardium and the myocardium. This inter-tissue crosstalk is an emerging and important integrative concept in cardiac development, supported by the recent description of fields of competence in the endocardium (Chang et al., 2004; Timmerman et al., 2004; Grego-Bessa et al., 2007), a finding compatible with the heterogeneity of region-specific myocardial signals and the ability of endocardial cells to respond to them. The four-chambered, fully-septated hearts of avians and mammals have the most sophisticated valve system of all vertebrates. Cardiac valves are crucial for coordination of an efficient blood supply to the body and lungs through two parallel circuits. Cardiac valves can be classified as atrioventricular (AV) and conoventricular (outflow tract, OFT). Heart valves are fibrous structures that originate, at least in part, from the endocardium that lines the corresponding myocardial segments; the endocardium of the atrioventricular and outflow tract regions is unique and has specific gene expression patterns. The valves are not completely functional until late gestation (Larsen, 2001) and are fully mature only after birth.