Multiscale modelling of Notch-mediated lateral induction

A published model of Notch-mediated lateral induction is re-implemented as a multiscale model using Compucell3D. The implications of the model for regulatory processes during the growth of the endocardial cushions are investigated. During embryonic heart development, Notch signaling operates by lateral induction to demarcate the endocardial cells capable of an epithelial to mesenchymal transition (EMT). This process underlies much of the inner structure of the heart, including the heart valves. Thus it is key to an understanding of congenital heart defects. Notch has a direct role to play in regulating endocardial cadherin proteins. The resulting loss of endocardial cohesion contributes to EMT. Thus cells with a higher Notch activation are more disposed to EMT. The simulations indicate that Notch-mediated lateral induction could provide a simple mechanism for preferential growth towards the centers of the endocardial cushions.