The placenta has been described as “an apposition of maternal and foetal tissue for the purposes of physiological exchange”1 . In the mouse this exchange occurs within a layer of the placenta termed the labyrinth. To meet the increasing metabolic demands of the growing foetus, the placenta develops an elaboration of villi, vascularized by foetal vessels and bathed in maternal blood, which dramatically increases the surface area for exchange. A highly organized transporting interhaemal membrane separates the maternal and foetal blood compartments and is comprised of three trophoblast layers; a layer of sinusoidal trophoblast giant cells (stgc) and two layers of syncytiotrophoblast (synT-I and II) overlying fetal endothelium. The inadequate development of villous architecture or aberrant organisation of the interhaemal membrane severely affects placental function and ensuing foetal development.
In an effort to improve our understanding of placental labyrinth formation we have characterised the placental phenotype of Ly6e deficient mice. Ly6e encodes a small molecular weight, GPI-linked glycoprotein of the Ly-6 family of cell surface proteins. We show that Ly6e is expressed within synT-I cells in a pattern reminiscent of Syna. Like Syna, genetic deletion of Ly6e is embryonic lethal by mid-gestation, a phenotype originally attributed to heart abnormalities2 . Our analysis demonstrates that Ly6e-/- placentae are abnormal, both in the gross organisation of the villous tree and in the ultrastructural organisation of the interhaemal membrane. In situ hybridisation shows trophoblast differentiation is not affected in Ly6e-/- placenta per se, but a reduction in villous branching is clearly evident. Further indicative of a morphogenesis defect, electron microscopy of Ly6e-/- interhaemal membranes reveals areas of disrupted syncytiotrophoblast fusion and an overall increase in barrier thickness, all suggesting profound deficiencies in placental function. Furthermore, these placental phenotypes precede the appearance of heart abnormalities, and are therefore the likely cause of lethality in these mice.