You are mostly electrical, and your cells use physical contact to decide if they are going to become a placenta or a person. This is the first meaningful decision any of us ever makes, occurring around day four or five of human development when the embryo is a tiny ball of cells called a morula. The decision is governed by geometry, mechanical tension, and a specific molecular cascade known as the Hippo pathway. We often think of development as a series of instructions being read from a manual (the DNA), but the genome doesn’t know where a cell is located in space. The cell has to figure that out for itself by “feeling” its neighbors, and the way it translates that physical sensation into a fate is through the suppression or activation of specific kinases.

This process is the foundation of everything that follows, including your ability to exist as a multicellular organism rather than a disorganized clump of tissue. If the Hippo pathway malfunctions during these first few days, the embryo fails to form the blastocyst (the stage where it implants in the uterus), and the pregnancy ends before the woman even knows she was pregnant.

The Geometry of the First Split

At the very beginning, you are a single cell (the zygote) that divides into two, then four, then eight. Up until the eight-cell stage, every cell is totipotent, meaning any one of them could theoretically become an entire human being if separated from the rest. The cells are loose, barely touching, and essentially identical in their gene expression. But at the eight-cell stage, something radical happens called compaction. The cells suddenly increase their adhesion to one another, maximizing their contact area and transforming from a loose cluster into a smooth, spherical ball.

This compaction is driven by E-cadherin, a protein that acts like molecular velcro, pulling the cells together and creating the first structural distinctions in your existence. For the first time, there is an “inside” and an “outside.” A cell in the middle of the ball is surrounded by other cells on all sides, experiencing pressure and contact from every direction. A cell on the surface has one side facing the external environment (the fluid in the fallopian tube or the culture media in a lab). This asymmetry is the signal that the Hippo pathway detects.

The cells on the outside will become the trophectoderm (TE), the specialized layer that forms the placenta and mediates the connection to the mother. The cells on the inside will become the Inner Cell Mass (ICM), which is the part that actually becomes the fetus. This is the first lineage split, the moment the extra-embryonic is separated from the embryonic. The decision is based entirely on position. If you take an outside cell and move it to the inside during this window, it will change its mind and become part of the ICM. Your first identity was determined by your zip code within the embryo.

The Hippo Mechanism: Turning Physics into Fate

How does a cell know it has a free surface? The answer lies in apical-basal polarity. Outside cells develop a “top” (apical) side and a “bottom” (basolateral) side. On the apical side, the cell assembles a complex of proteins, most notably aPKC (atypical protein kinase C) and Par proteins (Partitioning defective proteins). This apical cap is only possible because that side of the cell is not touching another cell.