Asymmetry in mechanosensitive gene expression during aortic arch morphogenesis

Abstract

Embryonic aortic arches (AA) are initially bilaterally paired, transitional vessels and failures in remodeling based on hemodynamic and growth-related adaptations cause a spectrum of congenital heart disease (CHD) anatomies. Identifying regulatory mechanisms and cross-talk between the genetic elements of these vessels are critical to understand the ethiology of CHD and refine predictive computational models. This study aims to screen expression profiles of fundamental biological pathways in AA at early stages of chick embryo morphogenesis and correlate them with our current understanding of growth and mechanical loading. Reverse transcription-quantitative PCR (RT-qPCR) was followed by correlation and novel peak expression analyses to compare the behaviour and activation period of the genes. Available protein networks were also integrated to investigate the interactions between molecules and highlight major hierarchies. Only wall shear stress (WSS) and growth-correlated expression patterns were investigated. Effect of WSS was seen directly on angiogenesis as well on structural and apoptosis-related genes. Our time-resolved network suggested that WSS-correlated genes coordinate the activity of critical growth factors. Moreover, differential gene expression of left and right AA might be an indicator of subsequent asymmetric morphogenesis. These findings may further our understanding of the complex processes of cardiac morphogenesis and errors resulting in CHD.