The end of cleavage is marked by the commencement of the differentiation of the organs. The first differentiation is the formation of the layers. These are three in number, being called respectively the ectoderm, endoderm and mesoderm, or, in embryos in which at their first appearance they lie like sheets one above the other, the epiblast, hypoblast and mesoblast. The layers are sometimes spoken of as the primary organs, and their importance lies in the fact that they are supposed to be generally homologous throughout the series of the Metazoa. This view, which is based partly on their origin and partly on their fate, had great influence on the science of comparative anatomy during the last thirty years of the 19th century, for the homology of the layers being admitted, they afforded a kind of final court of appeal in determining questions of doubtful homologies between adult organs. Great importance was therefore attached to them by embryologists, and both their mode of development and the part which they play in forming the adult organs were examined with the greatest care. It is very unusual for all the layers to be established at the same time. As a general rule the ectoderm and endoderm, which may be called the primary layers, come first, and later the mesoderm is developed from one or other of them. There are two main methods in which the first two are differentiated--invagination and delamination. The former is generally found in small eggs, in which the embryo at the close of cleavage assumes the form of a sphere, having a fluid or gelatinous material in its centre, and bounded externally by a thin layer of protoplasm, in which all the nuclei are contained. Such a sphere is called a blastosphere, and may be regarded as a spherical mass of protoplasm, of which the central portion is so much vacuolated that it seems to consist entirely of fluid. The central part of the blastosphere is called the segmentation cavity or blastocoel. The blastosphere soon gives rise, by the invagination of one part of its wall upon the other, and a consequent obliteration of the segmentation cavity, to a double-walled cup with a wide opening, which, however, soon becomes narrowed to a small pore. This cup-stage is called the gastrula stage; the outer wall of the gastrula is the ectoderm, and its inner the endoderm; while its cavity is the enteron, and the opening to the exterior the blastopore. Origin of the primary layers by delamination occurs universally in eggs with large yolks (Cephalopoda and many Vertebrata), and occasionally in others. In it cleavage gives rise to a solid mass, which divides by delamination into two layers, the ectoderm and endoderm. The main difference between the two methods of development lies in the fact that in the first of them the endoderm at its first origin shows the relations which it possesses in the adult, namely, of forming the epithelial wall of the enteric space, whereas in the second