Figure 8.

Working model of valve morphogenesis. DCHS1, LIX1L and Sept9 are expressed in undifferentiated mesenchymal cells during embryonic development that are randomly distributed throughout the tissue. As these cells proliferate and increase in density, they encounter neighboring cells and engage cadherin receptors, much like train cars hooking together on a railroad track (ECM). DCHS1-LIX1L-SEPT9 (DLS) complex promotes filamentous actin formation and cell elongation. All cargo attached to the cell membrane, such as integrins and the ECM, then passively assume a similar organization and shape as the cells. This results in aligned, elongated cells and tissues with a stratified ECM. Defects in any step of this process would be anticipated as resulting in disrupted actin organization, disorganized cells, leaflet thickening and progression to a valve pathology.