Figure 8

A model for FAK as a key mediator of trophoblast differentiation. During early human placental development, when pO₂ levels in the intervillous space are low, FAK expression and activity are positively regulated. Active FAK is localized to a transitional zone of extravillous trophoblast cells that are proliferative and migratory but not yet fully differentiated into an invasive phenotype. FAK is essential for shifting the balance between proliferation and differentiation (into an invasive phenotype) to favor proliferation during early placental differentiation. Upon exposure of trophoblast cells to higher pO₂ levels, FAK expression and activity decrease, and FAK’s mediation of signaling pathways is reduced so that differentiation of extravillous trophoblast cells toward an invasive pathway becomes favored.