When the early embryo consists of only two tissue layers, ectoderm and endoderm, a longitudinal thickening appears as the result of multiplication of the ectodermal cells. This thickening, the primitive streak, gives rise to the notochord and to the third basic layer, the mesoderm. The longitudinal axis of the embryo is first laid down by the formation of a cylindrical mass of cells, the notochord, proliferated from the primitive (Hensen) node at the anterior end of the streak. The notochord lies ventral to the developing central nervous system and forms the first supporting structure for the developing embryo.

In fishes such as the shark, cartilaginous vertebrae form around the notochord and to some extent compress it. It persists, nevertheless, as a continuous structure through the length of the vertebral column. In the higher vertebrates, including humans, the notochord is a temporary structure, persisting only as a minute canal in the bodies of the vertebrae and in the central part of the nucleus pulposus of the intervertebral disks.

As the notochord is being laid down, cells proliferate from each side of the primitive streak, forming the mesoderm, which spreads out laterally and, as a result of migration and multiplication of cells, soon comes to occupy most of the space between the ectoderm and the endoderm on each side of the notochord. The mesodermal sheets soon become differentiated into (1) a mass lying on each side of the notochord (paraxial mass) that undergoes segmentation into hollow blocks, the mesodermal somites, (2) a lateral plate that becomes separated into an outer layer, the somatopleuric mesoderm, against the future body wall and an inner layer, the splanchnopleuric mesoderm, against the endoderm of the future gut, and (3) an intermediate mass, the nephrogenic cord, which gives rise mainly to the genitourinary system.

The segmentation of the paraxial mesoderm is a fundamental feature of the development of the vertebrates. The axial skeleton and associated structures develop from part of the mesodermal somite; the appendicular skeleton arises from the somatopleuric mesoderm of the lateral plate. Each somite differentiates into (1) a lateral and superficial plaque, the dermatome, which gives rise to the integumentary tissue, (2) a deeper lateral mass, the myotome, which gives rise to the muscles, and (3) a medial ventral mass, the sclerotome. The sclerotomic cells from each pair of somites migrate until they enclose the notochord, separating it from the neural tube dorsally and from the aorta (the principal blood vessel) ventrally. The sclerotomic tissue retains its original segmentation and condenses to form the forerunner, or blastema, of the centrum of the future vertebra. From each posterolateral half of the condensation, extensions pass backward and eventually meet posteriorly around the neural tube to form the blastema of the neural (dorsal) arch of the vertebra. In the interspaces between adjacent myotomes of each side, an extension from each sclerotomic mass passes laterally and forward to form the costal, or rib, element. It is only in the thoracic (midbody) region that the costal elements develop into ribs. In the other regions the costal elements remain rudimentary (undeveloped).

The mesenchymal blastema of the future vertebra becomes chondrified; i.e., the mesenchymal cells are converted into cartilage cells. In this cartilaginous vertebra, ossification (bone-forming) centres appear, and the cartilage is gradually replaced by bone. The mesenchyme of the embryonic ribs also undergoes chondrification and later ossification. In the thoracic region, in which costal elements are best developed, a cartilaginous sternal bar forms, connecting the anterior, or growing, ends.

The appendicular skeleton begins to develop in the primitive limb bud in the core of mesenchyme that is derived directly from the unsegmented somatopleuric mesoderm. This mesenchyme condenses to form the blastemal masses of the future limb bones. Soon the mesenchyme becomes transformed into the cartilaginous precursors of the individual bones (except in the clavicle). The cartilaginous models determine the general shape and relative size of the bones. There is convincing evidence that the shape of the bones of higher vertebrates is determined by factors inherent in the tissues and that, once development has begun, extrinsic influences provide the proper conditions for maintaining the normal structure.

The first mesenchymal condensations of the appendicular skeleton are in the region of the future girdles; those for the shoulder girdle appear a little earlier than those for the pelvic girdle. The mesenchymal condensations for the other bones of the limbs appear in order of their proximity to the trunk.

Evolution of the vertebrate skeleton