Fig 7.

Model of regulation of EVT differentiation by GCM1. The mononuclear cytotrophoblasts (CT) in chorionic villi may proliferate and differentiate into a multinucleated syncytiotrophoblast (ST) layer or invasive extravillous trophoblasts (EVT). GCM1 can regulate ST differentiation through transactivation of syncytin-1, which interacts with its cognate receptor, the sodium-dependent neutral amino acid transporter type 2 (ASCT2), to facilitate cell-cell fusion. In addition, GCM1 can participate in EVT differentiation through transactivation of HtrA4, which may cleave fibronectin in the extracellular matrix (ECM) and facilitate cell migration and invasion. Importantly, HtrA4 may also cleave syncytin-1 to prevent cell-cell fusion of EVTs.