Genetic insights into trophoblast differentiation and placental morphogenesis

The placenta is comprised of an inner vascular network covered by an outer epithelium, called trophoblast, all designed to promote the delivery of nut rients to the fetus. Several specialized trophoblast cell subtypes arise du ring development to promote this function, including cells that invade the uterus to promote maternal blood flow to the implantation site, and other c ells that fuse into a syncytium, expand and fold to increase the surface ar ea for efficient transport. Mutation of many genes in mice results in embry onic mortality or fetal growth restriction due to defects in placental deve lopment. Several important principles about placental development have emer ged from these studies. First, distinct molecular pathways regulate the dif ferentiation of the various trophoblast cell subtypes. Second, trophoblast proliferation, differentiation and morphogenesis are highly regulated by in teractions with adjacent cell types. Finally the specific classes of mutant phenotypes observed in the placenta of knockout mice resemble those seen i n humans that are associated with preeclampsia and intrauterine growth rest riction.