Epithelia line most organs of the human body. They contribute to major bodily functions such as physically protecting organs (e.g. skin) or filtering media between compartments (e.g. kidney). To exert these functions, epithelia are able to buffer and adapt to physical stresses.
During its first days of development, the mammalian embryo forms its first epithelium, the trophectoderm (TE). The TE is an extraembryonic tissue enveloping a fluid-filled cavity and an inner cluster of pluripotent stem cells, which together constitute the blastocyst. The TE is essential to mammalian development and most often at fault when embryos fail to implant. Indeed, the TE is responsible for inflating the cavity, patterning embryonic tissues and invading the uterus. As the cavity forms, part of the TE remains in contact with inner cells and differentiates into the polar TE (pTE), whereas the TE surrounding the cavity becomes the mural TE (mTE). Therefore, the positioning of the cavity determines the first axis of symmetry of the mammalian embryo, which then sets the attachment point of the embryo. During this process, we have identified that local differences in cell adhesion or contractility can control the position of the cavity. Therefore, differences in physical properties among epithelial cells can position the cavity and lead to their differentiation. However, it remains unclear whether a pre-existing cue would predetermine this axis.
We hypothesize that epithelial physical properties govern cavity positioning and cell patterning. To test this and better understand how the physics of epithelia shapes tissues and organisms in vivo, we will study the transport properties, membrane properties and nuclear mechanics of the TE during preimplantation development. This will allow us to determine the relative contributions of physical properties to epithelial stretching and patterning.
