Biomechanical Cues Direct Valvulogenesis

The vertebrate embryonic heart initially forms with two chambers, a ventricle and an atrium, separated by the atrioventricular junction. Localized genetic and biomechanical information guides the development of valves, which function to ensure unidirectional blood flow. If the valve development process goes awry, pathology associated with congenital valve defects can ensue. Congenital valve defects (CVD) are estimated to affect 1-2% of the population and can often require a lifetime of treatment. Despite significant clinical interest, molecular genetic mechanisms that direct valve development remain incompletely elucidated. Cells in the developing valve must contend with a dynamic hemodynamic environment. A growing body of research supports the idea that cells in the valve are highly sensitive to biomechanical forces, which cue changes in gene expression required for normal development or for maintenance of the adult valve. This review will focus on mechanotransductive pathways involved in valve development across model species. We highlight current knowledge regarding how cells sense physical forces associated with blood flow and pressure in the forming heart, and summarize how these changes are transduced into genetic and developmental responses. Lastly, we provide perspectives on how altered biomechanical cues may lead to CVD pathogenesis.