Embryology

Evolution

The development of the human musculoskeletal system is an interesting demonstration of ontogeny recapitulating phylogeny. The genetic code that guides the continually changing body plan of the developing human results in a résumé of body plans of the various forms of our vertebrate ancestors from which fish, amphibians, reptiles, and mammals evolved. In their adult state, a number of living animals resemble some of the ancient ancestors of the central stem line. The knowledge of the fossil record of extinct forms and the comparative anatomy and physiology of living animals makes rational so many aspects of human development that would otherwise have to be regarded as completely wasteful and nonsensical, or both.

Amphioxus

The extant adult amphioxus, or lancelet, is considered to resemble an ancient ancestor of the vertebrates (see Plate 1-1 ). It is a fishlike animal, about 2 inches long, that has the basic body plan of the early human embryo. The central nervous system consists of a nerve cord resembling the portion of the human embryonic neural tube that becomes the spinal cord. The digestive, respiratory, excretory, and circulatory systems of the amphioxus also closely resemble those of the early human embryo. As in the early human embryo, the skeleton of the amphioxus consists of a notochord, a slender rod of turgid cells that runs the length of the body directly beneath the nerve cord, or neural tube. The muscular system of the amphioxus consists of individual muscle segments on each side of the body, known as myotomes or myomeres, which are similar in appearance to the myotomes of the early human embryo. The nerve cord of the amphioxus gives off a pair of nerves to each myotome, and the striated muscle fibers of the myotomes contract to produce the lateral bending movements of swimming.

Axial Skeleton

The axial skeleton includes the vertebrae, ribs, sternum, and skull. The first structure of the future axial skeleton to form is the notochord (see Plate 1-1 ). It appears in the midline of the embryonic disc at 15 days of development as a cord of cells budding off from a mass of ectoderm known as Hensen's node. The notochordal cells become temporarily intercalated in the endoderm, which forms the roof of the yolk sac. After separating from the endoderm, the notochord becomes a slender rod of cells running the length of the embryo between the neural tube and the developing gut.

The dorsal mesoderm on either side of the notochord becomes thickened and arranged into 42 to 44 pairs of cell masses known as somites (4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 8 to 10 coccygeal) between the 19th and 32nd day of development. The formation of these primitive segments, or somites, reflects the serial repetition of homologous parts known as metamerism, which is retained in many adult prevertebrates. The vertebrate embryo is fundamentally metameric, even though much of its segmentation is lost as development proceeds to the adult form. The first significant change in the somite of the human embryo is the formation of a cluster of mesenchymal cells, the sclerotome, on the ventromedial border of the somite (see Plate 1-2 ). The sclerotomal cells migrate from the somites and become aggregated about the notochord to ultimately give rise to the vertebral column and ribs (see Plate 1-3 ).

Vertebral Column and Ribs

During the fourth week of development, a clustering of sclerotomal cells derived from two adjacent somites on either side of the notochord becomes the primordium of the body, or centrum, of a vertebra. Soon after the body takes shape, paired concentrations of mesenchymal cells extend dorsally and laterally from the body to form the primordia of the neural arches and the costal processes. The costal process becomes a rib that articulates with the body and transverse process of the neural arch of the thoracic vertebrae (see Plate 1-4 ). The costal process becomes the anterior part of the transverse foramen of the cervical vertebrae, the transverse process of the lumbar vertebrae, and the lateral part of the sacrum. Occasionally, the costal process of the seventh cervical or the first lumbar vertebra becomes a supernumerary rib. Failure of fusion of the neural folds results in various types of spina bifida.

The vertebrae and ribs in the mesenchymal, or blastemal, stage are one continuous mass of cells. This stage is quickly followed by the cartilage stage, when the mesenchymal cells become chondrocytes and produce cartilage matrix during the seventh week, beginning in the upper vertebrae. By the time ossification begins at 9 weeks, the rib cartilages have become separated from the vertebrae.

The clustering of sclerotomal cells to form the bodies of the vertebrae establishes intervertebral fissures that fill with mesenchymal cells to become the intervertebral discs (see Plate 1-3 ). The notochord in the center of the developing intervertebral disc expands as its cells produce a large amount of mucoid semifluid matrix to form the nucleus pulposus. The mesenchymal cells surrounding the nucleus pulposus produce proteoglycans and collagen fibers to become the fibrocartilage anulus fibrosus of the intervertebral disc. At birth, the nucleus pulposus makes up the bulk of an intervertebral disc. From birth to adulthood, it serves as a shock-absorbing mechanism, but by 10 years of age the notochordal cells have disappeared and the surrounding fibrocartilage begins to gradually replace the mucoid matrix. The water-binding capacity and elasticity of the matrix are also gradually reduced.

The portion of the notochord surrounded by the developing body of a vertebra usually disappears completely before maturity. This is also true of the portions that become incorporated into the body of the sphenoid and the basilar part of the occipital bone. However, the portion of the notochord that normally becomes the nucleus pulposus in the intervertebral discs becomes the apical dental ligament, connecting the dens of the axis with the occipital bone. The dens evolved as an addition to the body of the first cervical vertebra, the atlas, in those reptiles that gave rise to mammals. The most primitive of mammals, the duck-billed platypus and the spiny anteater, have a large atlas body and a dens. In the human embryo, the atlas body and dens become dissociated as a unit from the rest of the atlas and fuse with the body of the second cervical vertebra, the axis (see Plate 1-5 ). This fusion results in a mature ring-shaped atlas with an anterior arch lacking a body.

At 5 weeks, a prominent tail containing coccygeal vertebrae is present in the human embryo (see Plate 1-3 ). A free-moving tail is characteristic of most adult vertebrates. However, the human tail is concealed by the growing buttocks and actually regresses to become the coccyx, which consists of four or five rudimentary vertebrae fused together.

Sternum

At 6 weeks, a pair of bands of mesenchymal cells, the sternal bars, appear ventrolaterally in the body wall (see Plate 1-5 ). They have no connection with the ribs or with each other, and their formation is independent of any sclerotomal derivatives. After the attachment of the upper ribs to the sternal bars, they fuse together progressively in a craniocaudal direction. At 9 weeks, the union of the bars, which have become cartilaginous, is complete. At the cranial end of the sternal bars, two suprasternal masses form and fuse with the future manubrium to serve as sites where the clavicles articulate. Influenced by the ribs, the cartilaginous body of the sternum becomes secondarily segmented into six sternebrae. Faulty fusion of the sternal bars in the midline results either in a cleft or perforated sternum or in a bifid xiphoid process.

Skull

The skeleton of the head consists of three primary components: (1) the capsular investments of the sense organs, (2) the brain case, and (3) the branchial arch skeleton (see Plate 1-6 ). Other than some exceptions of the branchial arch skeleton, these three primary components unite into a composite mammalian skull.

The notochord originally extends into the head of the embryo as far as the oropharyngeal membrane. Its termination later shifts to the caudal border of the hypophyseal fossa of the sphenoid bone. (The replacement of the notochord in the head region during evolution involved the formation of a cartilaginous cranium similar to that in the primitive fish of the shark type, which had a skeleton composed of only cartilage.) The earliest indication of skull formation in the human embryo is the concentration of mesenchyme about the notochord at the level of the hindbrain during the fifth and sixth weeks (see Plate 1-3 ). This mesenchymal skull formation extends forward to form a floor for the developing brain. By the seventh week, the skull begins to become cartilaginous as it completely or incompletely encapsulates the organs of olfaction (nasal capsule), vision (orbitosphenoid), and audition and equilibrium (otic capsule). This chondrocranium is essentially roofless.

As the evolving brain increased in size, additional rudiments were acquired to form a top to the braincase—the calvaria (skullcap). In bony fish, these were derived from the enlarged scales of the head region, which sank into the head and sheathed the chondrocranium to become the bones of the top and sides of the skull and the jaws. These encasing bones derived from the skin are known as dermal, or membrane, bones. In the human embryo, the mesenchymal membrane bone rudiments form the top and sides of the skull and the bones of the face and jaws. They never transform into cartilage; therefore, bone forms directly within the membranous tissue. Most of the membrane bone rudiments become independent bones, but a few become parts of bones formed in the chondrocranium.

The branchial arch skeleton is derived from the embryonic counterparts of the gill arches that support the mouth and pharynx of present-day adult fish and tailed amphibians. The most primitive skeletal rudiments of the branchial arches develop from neural crest cells that migrate into the arches, not from the mesoderm of the arches. The neural crest rudiments become cartilaginous and are retained as cartilage in present-day adult cartilaginous fish, such as the shark, to support the jaw and aqueous respiratory system. In the evolutionary transformation from water breathing to air breathing, much of the skeleton of the aqueous respiratory system was modified to become parts of the air respiratory system, as well as of the modified acoustic apparatus. The human embryo goes through the essential structural stages of this evolutionary water-breathing to air-breathing transformation. Some of the cartilages remain in the adult human (laryngeal cartilages), whereas others become bone (hyoid, styloid process, and ossicles of the middle ear). The branchial arch components originally subserved the function of mastication as well as that of respiration. Although the primitive cartilages of the first branchial arches become the skeletons of the upper and lower jaws in cartilaginous fish, they do not do so in humans, in whom the maxillae and mandible are derived from membrane bones.

Because the brain grows large before birth, the calvaria is much larger than the facial skeleton in the neonate with a ratio of 8 : 1, compared with a ratio of 2 : 1 in the adult (see Plate 1-7 ).

Appendicular Skeleton

The appendicular skeleton consists of the pectoral and pelvic girdles and the bones of the free appendages attached to them. The paired appendages of land vertebrates evolved from the paired fins of fish. The development of the human limbs is a résumé of their evolution.

The upper limb buds appear first, differentiate sooner, and attain their final relative size earlier than the lower limbs (see Plates 1-3, 1-8, and 1-9 ). Not until birth do the lower limbs equal the upper limbs in length (see Plate 1-7 ). However, throughout childhood, the lower limbs elongate faster than the upper limbs. In essence, an upper limb was never a lower limb, and vice versa; each has its own unique evolutionary and developmental history. Even so, it is interesting that the structures of the mature upper and lower limbs have a number of similarities. They are most similar during the earliest stages of development, when both sets of finlike appendages point caudally. They then become paddle-like and project outward almost at right angles to the body wall. After this, they bend at the elbow and knee directly anteriorly, so that the elbow and knee point laterally, or outward, and the palm and sole face the trunk. Then a series of major changes occurs that causes the upper and lower limbs to differ markedly both structurally and functionally (see Plate 1-8 ). By the seventh week, both undergo a 90-degree torsion about their long axes, but in opposite directions, so that the elbow points caudally and the knee points cranially. Accompanying this torsion is a permanent twisting of the entire lower limb, which results in its cutaneous innervation assuming a twisted, “barber pole” arrangement (see Plate 1-9 ). This would be similar to twisting the upper limb so that the forearm and hand become fully and permanently pronated.

The limb buds appear during the fourth week and consist of a core of condensed mesenchyme covered with an epidermal cap, the apical ectodermal ridge. They are functionally related in a two-way process of induction: the mesenchyme induces the development and maintenance of the ridge, which in turn gives the mesenchymal cells the “competence” to form the skeletal rudiments. Any genetic breakdown of differentiating cells or the presence of a teratogenetic substance that interferes with this two-way process of induction results in various limb malformations, such as amelia (total failure of limb development), hemimelia (failure of development of distal parts of limbs), or phocomelia (failure of development of the bulk of the limb but not of its distal part).

Once the appendicular skeleton starts to develop, the progress is rapid. Early in the sixth week, only vague concentrations of mesenchyme represent the primordia of future bones. By the end of the sixth week, these cellular concentrations are sufficiently molded so that some of the larger future bones can be detected. During the seventh week, the primordia of many of the smaller bones of the hand and foot are present.

By the eighth week, well-molded cartilage rudiments represent all the major future bones of the appendicular skeleton.