Ventricular Septal Defects: Molecular Pathways and Animal Models

Ventricular septationVentricularseptation is a complex process which involves the major genes of cardiac developmentCardiacdevelopment, acting on myocardial cells from first and second heart fields, and on mesenchymal cells from endocardial cushionsEndocardium, endocardialendocardial cushion. These genes, coding for transcription factors, interact with each other, and their differential expression conditions the severity of the phenotype. In this chapter, we will describe the formation of the ventricular septumVentricularseptum in the normal heart, as well as the molecular mechanisms leading to the four main anatomic types of ventricular septal defects: outlet, inlet, muscular, and central perimembranous, resulting from failure of development of the different parts of the ventricular septumVentricularseptum. Experiments on animal models, particularly transgenic mouse lines, have helped us to decipher the molecular determinants of ventricular septationVentricularseptation. However, a precise description of the anatomic phenotypes found in these models is mandatory to achieve a better comprehension of the complex mechanisms responsible for the various types of VSDs.