Cellular patterning during embryoid body formation. Around day 2, cells on the surface of the EB form a layer of primitive endoderm which exhibits an epithelial morphology with an increased expression of E-cadherin and a sensitive response to FGF signaling. These cells deposit a basement membrane which is rich in laminin and collagen IV. Cells adjacent to the basement membrane receive survival signals, whereas cells without contact undergo caspase-dependent apoptosis. Cavitation inside the EB forms a yolk sac-like structure and results in the formation of a columnar epithelium. Cells between the primitive endoderm and the columnar epithelium are highly responsive to different signaling pathways, including Wnt, Nodal, and BMP signaling.