Hearts and bones: Shared regulatory mechanisms in heart valve, cartilage, tendon, and bone development

The mature heart valves are dynamic structures composed of highly organized cell lineages and extracellular matrices. The discrete architecture of connective tissue within valve leaflets and supporting structures allows the valve to withstand life-long functional demands and changes in hemodynamic forces and load. The dysregulation of ECM organization is a common feature of heart valve disease and can often be linked to genetic defects in matrix protein structure or developmental regulation. Recent studies have identified specific regulatory pathways that are active in the developing valve structures and also control cartilage, tendon, and bone development. This review will focus on the regulatory hierarchies that control normal and abnormal heart valve development in parallel with other connective tissue cell types.