“…Apart from their role in shielding the embryo from the exterior, superficial cells differ from deep cells in many other ways. Superficial and deep cells do not mix until later in development (Keller, 1978;Smith and Malacinski, 1983;Hartenstein, 1989;Minsuk and Keller, 1997) and they follow different cell fates, express different genes and have different roles in gastrulation (Keller, 1975;Minsuk and Keller, 1997;Keller, 1976;Shih and Keller, 1992;Keller et al, 1985;Glinka et al, 1996;Smith et al, 1995;Sive and Bradley, 1996;Deblandre et al, 1999). Thus, the formation of an outer epithelial cell layer and one or more, internal non-epithelial cell layers, and the developmental distinction between them, is one of the fundamental differentiations in the early embryo.…”