Skeletal System

Skeletal System

The skeletal system develops from
paraxial and lateral plate (somatic layer) mesoderm neural crest.

Somites differentiate into Sclerotome and dermomyotome.

At the end of the fourth week, sclerotome cells become polymorphous and form a loosely woven tissue, the Mesenchyme, or embryonic connective tissue . Mesenchymal cells may become fibroblasts, chondroblasts, or osteoblasts (bone-forming cells). mesenchyme in the somatic mesoderm layer of the body wall contributes mesoderm cells for formation of the pelvic and shoulder girdles and the long bones of the limbs and sternum. Neural crest cells in the head region also differentiate into mesenchyme and participate in formation of bones of the face and skull. Occipital somites and somitomeres also contribute to formation of the cranial vault and base of the skull.

Bone formation

In some bones, such as the flat bones of the skull, mesenchyme in the dermis differentiates directly into bone, a process known as intramembranous ossification. In most bones, however, mesenchymal cells first give rise to hyaline cartilage models, which in turn become ossified by Endochondral ossification.

Endochondral bone formation

A. Mesenchyme cells begin to condense and differentiate into chondrocytes. B. Chondrocytes form a cartilaginous model of the prospective bone.

Endochondral bone formation

C. Blood vessels invade the center of the cartilaginous model, bringing osteoblasts (black cells) and restricting proliferating chondrocytic cells to the ends (epiphyses) of the bones. Chondrocytes toward the shaft side (diaphysis) undergo hypertrophy and apoptosis as they mineralize the surrounding matrix. D. Later, as blood vessels invade the epiphyses, secondary ossification centers form. Growth of the bones is maintained by proliferation of chondrocytes in the growth plates

The skull can be divided into two parts:

the Neurocranium, which forms a protective case around the brain, and the Viscerocranium, which forms the skeleton of the face.

Neurocranium 

The neurocranium is divided into two portions: A the membranous part, consisting of flat bones, which surround the brain as a vault B ) the cartilaginous part, or Chondrocranium, which forms bones of the base of the skull.

Membranous Neurocranium

Mesenchyme from neural crest cells and paraxial mesoderm. invests the brain and undergoes Membranous ossification. The result is formation of a number of flat, membranous bones that are characterized by the presence of needle-like bone spicules which radiate from primary ossification centers toward the periphery . With further growth during fetal and postnatal life, membranous bones enlarge by apposition of new layers on the outer surface and by simultaneous osteoclastic resorption from the inside.

Newborn Skull(sutures & fontanelles)

At birth, the flat bones of the skull are separated from each other by narrow seams of connective tissue, the sutures, which are also derived from two sources: neural crest cells (sagittal suture) and paraxial mesoderm (coronal suture). fontanelles : sutures are wide at points where more than two bones meet. The most prominent of these is the anterior fontanelle, which is found where the two parietal and two frontal bones meet. Sutures and fontanelles allow the bones of the skull to overlap (molding) during birth. Soon after birth, membranous bones move back to their original positions, and the skull appears large and round. In fact, the size of the vault is large compared with the small facial region.

Newborn Skull

Several sutures and fontanelles remain membranous for a considerable time after birth. The posterior fontanelle closes about 3 months after birth; the anterior fontanelle closes about the middle of the second year. Many of the sutures disappear during adult life.



Newborn Skull
The bones of the vault continue to grow after birth because the brain grows. Although a 5- to 7-year-old child has nearly all of his or her cranial capacity, some sutures remain open until adulthood.
After birth, palpation of the anterior fontanelle may give valuable information as to whether ossification of the skull is proceeding normally and Whether intracranial pressure is normal.

Cartilaginous Neurocranium or Chondrocranium

initially consists of a number of separate cartilages. Prechordal chondrocranium :Those that lie in front of the rostral limit of the notochord, which ends at the level of the pituitary gland in the center of the sella turcica, they are derived from neural crest cells. chordal chondrocranium: Those that lie posterior to rostral limit of the notochord . They arise from occipital sclerotomes formed by paraxial mesoderm . The base of the skull is formed when these cartilages fuse and ossify by endochondral ossification

Viscerocranium 

consists of the bones of the face which is formed mainly from the first two pharyngeal arches . The first arch gives rise to a dorsal portion, the maxillary process, which extends forward beneath the region of the eye and gives rise to the maxilla, the zygomatic bone, and part of the temporal bone . The ventral portion, the mandibular process, contains the Meckel cartilage. Mesenchyme around the Meckel cartilage condenses and ossifies by membranous ossification to give rise to the mandible. The Meckel cartilage disappears except in the sphenomandibular ligament. The dorsal tip of the mandibular process, along with that of the second pharyngeal arch, later gives rise to the incus, the malleus, and the stapes . Ossification of the three ossicles begins in the fourth month, making these the first bones to become fully ossified.

Skeletal structures of the head and face Mesenchyme for formation of the bones of the face is derived from neural crest cells, including the nasal and lacrimal bones (blue), paraxial mesoderm (somites and somitomeres) (red), and lateral plate mesoderm (yellow).

At first, the face is small in comparison with the neurocranium because of the (a) virtual absence of the paranasal air sinuses and (b) the small size of the bones, particularly the jaws. With the appearance of teeth and development of the air sinuses, the face loses its babyish characteristics.

Clinical Correlates

Neural Crest Cells : they are often a target for teratogens craniofacial abnormalities are common birth defects
Cranioschisis : the cranial vault fails to form and brain tissue exposed to amniotic fluid degenerates, resulting in Anencephaly. is due to failure of the cranial neuropore to close Children with such severe skull and brain defects cannot survive. cranial meningocele and meningoencephalocele : small defects in the skull through which meninges and/or brain tissue herniate . In such cases, the extent of neurological deficits depends on the amount of damage to brain tissue.



Craniosynostosis
is caused by premature closure of one or more sutures . the shape of the skull depends on which of the sutures closed prematurely. Early closure of the sagittal suture (57% of cases) results in frontal and occipital expansion, and the skull becomes long and narrow .

Microcephaly 

is usually an abnormality in which the brain fails to grow and the skull fails to expand. Many children with microcephaly are severely retarded.

Limbs Limb Growth and Development

At the end of the fourth week of development, limb buds become visible as outpocketings from the ventrolateral body wall . Initially, they consist of a mesenchymal core derived from the somatic layer of lateral plate mesoderm that will form the bones and connective tissues of the limb, covered by a layer of cuboidal ectoderm.

Apical ectodermal ridge (AER)

Ectoderm at the distal border of the limb thickens and forms the Apical ectodermal ridge (AER) . This ridge exerts an inductive influence on adjacent mesenchyme, causing it to remain as a population of undifferentiated, rapidly proliferating cells, the progress zone. As the limb grows, cells farther from the influence of the AER begin to differentiate into cartilage and muscle. In this manner, development of the limb proceeds proximodistally.

In 6-week-old embryos, the terminal portion of the limb buds becomes flattened to form the hand- and footplates and is separated from the proximal segment by a circular constriction . Later, a second constriction divides the proximal portion into two segments, and the main parts of the extremities can be recognized .

Fingers and toes are formed

A. At 48 days. Cell death in the apical ectodermal ridge creates a separate ridge for each digit. B. At 51 days. Cell death in the interdigital spaces produces separation of the digits. C. At 56 days. Digit separation is complete

Development of the upper and lower limbs is similar except that

morphogenesis of the lower limb is approximately 1 to 2 days behind that of the upper limb. Also, during the seventh week of gestation, the limbs rotate in opposite directions. The upper limb rotates 90 degrees laterally, so that the extensor muscles lie on the lateral and posterior surface and the thumbs lie laterally, whereas the lower limb rotates approximately 90 degrees medially, placing the extensor muscles on the anterior surface and the big toe medially.



mesenchyme in the buds begins to condense, and these cells differentiate into chondrocytes. By the sixth week of development, the first hyaline cartilage models are formed by these chondrocytes Joints are formed in the cartilaginous condensations when chondrogenesis is arrested, and a joint interzone is induced. Cells in this region increase in number and density, and then a joint cavity is formed by cell death. Surrounding cells differentiate into a joint capsule.

Ossification of the bones of the extremities

Ossification of the bones of the extremities, Endochondral ossification, begins by the end of the embryonic period. Primary ossification centers are present in all long bones of the limbs by the 12th week of development. From the primary center in the shaft or Diaphysis of the bone, endochondral ossification gradually progresses toward the ends of the cartilaginous model .
At birth, the diaphysis of the bone is usually completely ossified, but the two ends, the epiphyses, are still cartilaginous. Shortly thereafter, ossification centers arise in the epiphyses. Temporarily, a cartilage plate remains between the diaphyseal and epiphyseal ossification centers. This plate, the Epiphyseal plate, plays an important role in growth in the length of the bones. Endochondral ossification proceeds on both sides of the plate). When the bone has acquired its full length, the epiphyseal plates disappear, and the epiphyses unite with the shaft of the bone. In long bones, an epiphyseal plate is found on each extremity; in smaller bones, such as the phalanges, it is found only at one extremity; and in irregular bones, such as the vertebrae, one or more primary centers of ossification and usually several secondary centers are present

Clinical Correlates Bone Age 1.

Radiologists use the appearance of various ossification centers to determine whether a child has reached his or her proper maturation age. Useful information about bone age is obtained from ossification studies in the hands and wrists of children. Prenatal analysis of fetal bones by ultrasonography provides information about fetal growth and gestational age.

2. Limb Defects

partial ) meromelia) or complete absence) amelia ) of one or more of the extremities. Although these abnormalities are rare and mainly hereditary, cases of teratogen-induced limb defects have been documented. For example, many children with limb malformations were born between 1957 and 1962. Many mothers of these infants had taken thalidomide, a drug widely used as a sleeping pill and antinauseant. It was subsequently established that thalidomide causes a characteristic syndrome of malformations consisting of absence or gross deformities of the long bones, intestinal atresia, and cardiac anomalies. Since the drug is now being used to treat AIDS and cancer patients, there is concern that its return will result in a new wave of limb defects. Studies indicate that the most sensitive period for teratogen-induced limb malformations is the fourth and fifth weeks of development.


Sometimes the digits are shortened (brachydactyly). If two or more fingers or toes are fused, it is called syndactyly .Normally, mesenchyme between prospective digits in hand- and footplates is removed by cell death (apoptosis). In 1 per 2,000 births this process fails, and the result is fusion between two or more digits.

The presence of extra fingers or toes is called polydactyly . The extra digits frequently lack proper muscle connections. Abnormalities involving polydactyly are usually bilateral, whereas absence of a digit (ectrodactyly), such as a thumb, usually occurs unilaterally.

Cleft hand and foot (lobster claw deformity)

consists of an abnormal cleft between the second and fourth metacarpal bones and soft tissues. The third metacarpal and phalangeal bones are almost always absent, and the thumb and index finger and the fourth and fifth fingers may be fused The two parts of the hand are somewhat opposed to each other and act like a lobster claw.

Clubfoot

usually accompanies syndactyly. The sole of the foot is turned inward, and the foot is adducted and plantar flexed. It is observed mainly in male newborns and in some cases is hereditary. Abnormal positioning of the legs in utero may also cause clubfoot.

Congenital absence or deficiency of the radius

is usually a genetic abnormality observed with malformations in other structures, such as craniosynostosis–radial aplasia syndrome. Associated digital defects, which may include absent thumbs and a short curved ulna, are usually present.

Amniotic bands

may cause ring constrictions and amputations of the limbs or digits. The origin of bands is not clear, but 1. they may represent adhesions between the amnion and affected structures in the fetus. 2.or the bands may originate from tears in the amnion that detach and surround part of the fetus.

Congenital hip dislocation

consists of underdevelopment of the acetabulum and head of the femur. It is rather common and occurs mostly in female newborns. Although dislocation usually occurs after birth, the abnormality of the bones develops prenatally. Since many babies with congenital hip dislocation are breech deliveries, it has been thought that breech posture may interfere with development of the hip joint. It is frequently associated with laxity of the joint capsule.

Vertebrae and the Vertebral Column

During the fourth week, sclerotome cells migrate around the spinal cord and notochord to merge with cells from the opposing somite on the other side of the neural tube

Resegmentation

the caudal half of each sclerotome grows into and fuses with the cephalic half of each subjacent sclerotome. Thus, each vertebra is formed from the combination of the caudal half of one somite and the cranial half of its neighbor



Intervertebral disc :Mesenchymal cells between cephalic and caudal parts of the original sclerotome segment do not proliferate but fill the space between two precartilaginous vertebral bodies. Although the notochord regresses entirely in the region of the vertebral bodies, it persists and enlarges in the region of the intervertebral disc. Here it contributes to the Nucleus pulposus, which is later surrounded by circular fibers of the annulus fibrosus. Combined, these two structures form the Intervertebral disc

Resegmentation of sclerotomes into definitive vertebrae causes :

the myotomes to bridge the intervertebral discs, and this alteration gives them the capacity to move the spine intersegmental arteries, at first lying between the sclerotomes, now pass midway over the vertebral bodies. Spinal nerves come to lie near the intervertebral discs and leave the vertebral column through the intervertebral foramina.

Clinical Correlates Vertebral Defects

scoliosis (lateral curving of the spine): two successive vertebrae fuse asymmetrically or have half a vertebra missing cleft vertebra (spina bifida): imperfect fusion or nonunion of the vertebral arches. Spina bifida can be detected prenatally by ultrasound, and if neural tissue is exposed, amniocentesis can detect elevated levels of α-fetoprotein in the amniotic fluid (a) spina bifida occulta may involve only the bony vertebral arches, leaving the spinal cord intact. (b)spina bifida cystica, in which the neural tube fails to close, vertebral arches fail to form, and neural tissue is exposed.

Ribs and Sternum

Ribs form from costal processes of thoracic vertebrae and thus are derived from the sclerotome portion of paraxial mesoderm. The sternum develops independently in somatic mesoderm in the ventral body wall. Two sternal bands are formed on either side of the midline, and these later fuse to form cartilaginous models of the manubrium, sternebrae, and xiphoid process.