Development Of The Musculoskeletal System PDF

DEVELOPMENT OF THE SKELETAL SYSTEM 1 CONTENT Organisation of the mesoderm Paraxial, intermediate and lateral plate mesoderm Somitomeres and somites Sclerotome and dermomyotome Development of the skull Newborn skull Clinical correlates...

DEVELOPMENT OF THE SKELETAL SYSTEM 1 CONTENT Organisation of the mesoderm Paraxial, intermediate and lateral plate mesoderm Somitomeres and somites Sclerotome and dermomyotome Development of the skull Newborn skull Clinical correlates 2 Development of the limbs Development of the vertebral column, ribs and sternum. Molecular regulations of bone development Clinical correlates. 3 ORGANISATION OF THE MESODERM 4 More laterally, the mesoderm layer remains thin and is known as the lateral plate Mesoderm. With the appearance and coalescence of intercellular cavities in the lateral plate, this tissue is divided into two layers; Somatic or parietal mesoderm layer Splanchnic or visceral mesoderm layer 5 Together, these layers line a newly formed cavity, the intraembryonic cavity, which is continuous with the extraembryonic cavity on each side of the embryo. Intermediate mesoderm connects paraxial and lateral plate mesoderm 6 By the beginning of the third week, Paraxial mesoderm is organized into segments of tissue blocks known as somitomeres, which first appear in the cephalic region of the embryo, and their formation proceeds cephalocaudally. 7 Each somitomere consists of mesodermal cells arranged in concentric whorls around the center of the unit In the head region, somitomeres form in association with segmentation of the neural plate into neuromeres and contribute to mesenchyme in the head 8 From the occipital region caudally, somitomeres further organize into somites. There are four occipital, eight cervical, 12 thoracic, five lumbar, five sacral, and eight to 10 coccygeal pairs. The first occipital and the last five to seven coccygeal somites later disappear, while the remaining somites form the axial skeleton 9 During this period of development, the age of the embryo is expressed in number of somites. 10  Age of Embryo and Number of Somites AGE (DAYS) NO. OF SOMITES 20 1–4 21 4–7 22 7 – 10 23 10 – 13 24 13 – 17 25 17 – 20 26 20 – 23 27 23 – 26 28 26 – 29 30 29 - 35 11 Somites differentiate to give three sets of precusors: Sclerotome( Ventromedial part) -Axial Skeleton Dermamyotome( dorsolateral part) Myotome - Striated musculature of neck, trunk and extremities Dermotome - Subcutaneous tissue and skin 12 Somite differentiation Sclerotome → Cartilage and bone Dermomyotome → Dermatome - skin → Myotome - muscle 13 Neural crest cells in the head region also differentiate into mesenchyme and participate in formation of bones of the face and skull. In summary, the skeletal system develop from the paraxial mesoderm, somatic lateral plate mesoderm and neural crest cells 14 Occipital somites and somitomeres also contribute to formation of the cranial vault and base of the skull. 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 15  BONE DEVELOPMENT Intramembranouse ossification Endochondral ossification Organisation of the skeletal system into Axial Appendicular system 16  THE SKULL The skull can be divided into two parts: The neurocranium, which forms a protective case around the brain The viscerocranium,forms the skeleton of the face. 17  The neurocranium is most conveniently 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. The membranous portion of the skull is derived from neural crest cells and paraxial mesoderm Mesenchyme from these two sources invests the brain and undergoes membranous ossification 18 The result is formation of a number of flat, membranous bones that are characterized by the presence of needle-like bone spicules. These spicules progressively radiate from primary ossification centers toward the periphery. 19  NEWBORN SKULL 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) Paraxial mesoderm (coronal suture) 20 At points where more than two bones meet, sutures are wide and are called fontanelles The most prominent of these is the anterior fontanelle, which is found where the two parietal and two frontal bones meet. 21 The viscerocranium, which consists of the bones of the face, is formed mainly from the first two pharyngeal arches. 22  CLINICAL CORRELATES Sutures and fontanelles allow the bones of the skull to overlap (molding) during birth. In the first few years 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. 23 In some cases the cranial vault fails to form (cranioschisis), and brain tissue exposed to amniotic fluid degenerates, resulting in anencephaly. Cranioschisis is due to failure of the cranial neuropore to close. Children with such severe skull and brain defects cannot survive. 24 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 Croniosynostosis is cranial abnormalitles is caused by premature closure of one or more sutures 25  DEVELOPMENT OF THE LIMBS At the end of the fourth week of development, limb buds become visible as outpocketing's from the ventro-lateral body wall of somatic layer of the lateral plate mesoderm. Ectoderm at the distal border of the limb thickens and forms the apical ectodermal ridge (AER) 26 27 This ridge exerts an inductive influence on adjacent mesenchyme, causing it to remain as a population of undifferentiated, rapidly proliferating cells, called 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. 28 29 In 6-week-old embryos the terminal portion of the limb buds becomes flattened to form the handplates and footplates Fingers and toes are formed when cell death in the AER separates this ridge into five parts 30 Further formation of the digits depends on their continued outgrowth under the influence of The five segments of ridge ectoderm Condensation of the mesenchyme to form cartilaginous digital rays The death of intervening tissue between the rays 31 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 32 Also, during the seventh week of gestation the limbs rotate in opposite directions.; The upper limb rotates 90◦ 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◦ medially, placing the extensor muscles on the anterior surface and the big toe medially. This rotation is important for bipedalism 33 While the external shape is being established, mesenchyme in the buds begins to condense and these cells differentiate into chondrocytes By the 6th week of development the first hyaline cartilage models, foreshadowing the bones of the extremities, are formed by these chondrocytes 34 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. 35  CLINICAL CORELATES Bone Age: 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 36 Abnormalities of the limbs vary greatly, and they may be represented by partial (meromelia) or complete absence (amelia) of one or more of the extremities. Sometimes the long bones are absent, and rudimentary hands and feet are attached to the trunk by small, irregularly shaped bones (phocomelia, a form of meromelia) Sometimes all segments of the extremities are present but abnormally short (micromelia). 37 A different category of limb abnormalities consists of extra fingers or toes (polydactyly) The absence of a digit such as a thumb (ectrodactyly) Abnormal fusion is usually restricted to the fingers or toes (syndactyly) 38 VERTEBRAL COLUMN, RIBS AND STERNUM During the fourth week of development, cells of the sclerotomes shift their position to surround both the spinal cord and the notochord These contribute to the formation of the vertebral column The notochord regresses in the region between each segment of the vertebral column to form the nucleus pulposus and it is surrounded by intersegmental tissue called the annulus fibrosus 39 The nucleus pulposus together with the annulus fibrosus forms the intervertebral disc. Ribs form from costal processes of thoracic vertebrae and thus are derived from; The sclerotome portion of paraxial mesoderm. 40 41  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. 42  CLINICAL CORRELATES The process of formation and rearrangement of segmental sclerotomes into definitive vertebrae is complicated, and it is fairly common to have two successive vertebrae fuse asymmetrically or have half a vertebra missing, a cause of scoliosis (lateral curving of the spine) 43 One of the most serious vertebral defects is the result of imperfect fusion or nonunion of the vertebral arches. Such an abnormality, known as cleft vertebra (spina bifida). It may involve only the bony vertebral arches, leaving the spinal cord intact. In these cases the bony defect is covered by skin, and no neurological deficits occur (spina bifida occulta). A more severe abnormality is spina bifida cystica, in which the neural tube fails to close, vertebral arches fail to form, and neural tissue is exposed. 44 MOLECULAR REGULATIONS OF BONE DEVELOPMENT Positioning of the limbs along the craniocaudal axis in the flank regions of the embryo is regulated by the HOMEOBOX genes expressed along this axis. Hox genes also regulates shape and type of bone to be form Once positioning along the craniocaudal axis is determined, growth must be regulated along the proximodistal, anteroposterior, and dorsoventral axes by the fibroblast growth factors FGF and fibroblast growth factor receptors Once outgrowth is initiated, bone morphogenetic proteins (BMPs), expressed in ventral ectoderm, induce formation of the AER by signaling through the homeobox gene 45 Expression of Radical fringe (a homologue of Drosophila fringe), in the dorsal half of the limb ectoderm, restricts the location of the AER to the distal tip of the limbs. Anterior posterior patterning is regualted by sonic hedghog 46  THE MUSCULAR SYSTEM With the exception of some smooth muscle tissue the muscular system develops from the mesodermal germ layer and consists of skeletal, smooth, and cardiac muscle. Skeletal muscle is derived from paraxial mesoderm, which forms somites from the occipital to the sacral regions and somitomeres in the head. Smooth muscle differentiates from splanchnic mesoderm surrounding the gut and its derivatives and from ectoderm (pupillary, mammary gland, and sweat gland muscles). Cardiac muscle is derived from splanchnic mesoderm surrounding the heart tube. 47 Studies show that myogenic precursor cells originate from the somatic and splanchnic mesoderm and also from the ventral dermomyotome of somites in response to molecular signals from nearby tissues. The first indication of myogenesis (muscle formation) is the elongation of the nuclei and cell bodies of mesenchymal cells as they differentiate into myoblasts. Soon these primordial muscle cells fuse to form elongated, multinucleated, cylindrical structures- myotubes. 48 From the occipital region caudally, somites form and differentiate into the sclerotome, dermatome, and two muscle-forming regions 49 One of these is in the dorsolateral region of the somite. It expresses the muscle-specific gene MYO-D and migrates to provide progenitor cells for limb and body wall (hypomeric) musculature The other region lies dorsomedially, migrates ventral to cells that form the dermatome, and forms the myotome. This region, which expresses the muscle-specific gene MYF5, forms epimeric musculature 50 51 During differentiation, precursor cells, the myoblasts, fuse and form long, multinucleated muscle fibers. Myofibrils soon appear in the cytoplasm, and by the end of the third month, cross-striations typical of skeletal muscle appear. A similar process occurs in the seven somitomeres in the head region rostral to the occipital somites. Somitomeres remain loosely organized structures, however, never segregating into sclerotome and dermomyotome segments. 52 53 Molecular Regulations Of Muscle Development BMP4 and probably FGFs from lateral plate mesoderm, together with WNT proteins from adjacent ectoderm, signal the dorsolateral cells of the somite to express the muscle-specific gene MYO-D. BMP4 secreted by overlying ectoderm induces production of WNT proteins by the dorsal neural tube, and these proteins cause dorsomedial cells of the somite to activate MYF5, another muscle specific gene 54 Both of these genes are members of the MYO-D muscle-specific family, which also includes the myogenin and MRF4 genes. MYO-D and MYF5 proteins activate the genes for myogenin and MRF5, which in turn promote formation of myotubes and myofibers. All MYO-D family members have DNA binding sites and act as transcription factors to regulate downstream genes in the muscle differentiation pathway. 55 By the end of the fifth week prospective muscle cells are collected into two parts: A small dorsal portion, the epimere, formed from the dorsomedial cells of the somite that reorganized as myotomes A larger ventral part, the hypomere, formed by migration of dorsolateral cells of the somite Nerves innervating segmental muscles are also divided into a dorsal primary ramus for the epimere and a ventral primary ramus for the hypomere and these nerves will remain with their original muscle segment throughout its migration. 56 57 Myoblasts of the epimeres form the extensor muscles of the vertebral column, and those of the hypomeres give rise to muscles of the limbs and body wall Myoblasts from cervical hypomeres form the scalene, geniohyoid, and prevertebral muscles. Those from thoracic segments split into three layers, which in the thorax are represented by the External intercostal, Internal intercostal, Innermost intercostal or transversus thoracis muscle 58 In the abdominal wall these three muscle layers consist of the external oblique, the internal oblique, and the transversus abdominis muscles. The ribs cause the muscles in the wall of the thorax to maintain their segmental character, whereas muscles in the various segments of the abdominal wall fuse to form large sheets of muscle tissue. Myoblasts from the hypoblast of lumbar segments form the quadratus lumborum muscle, and those from sacral and coccygeal regions form the pelvic diaphragm and striated muscles of the anus. 59 60  Head Musculature All voluntary muscles of the head region are derived from paraxial mesoderm(somitomeres and somites), including musculature of the tongue(from occipital somites), and the eye muscles (except that of the iris, which is derived from optic cup ectoderm), and that associated with the pharyngeal (visceral) arches Patterns of muscle formation in the head are directed by connective tissue elements derived from neural crest cells. 61  Limb Musculature The first indication of limb musculature is observed in the seventh week of development as a condensation of mesenchyme near the base of the limb buds The mesenchyme is derived from dorsolateral cells of the somites that migrate into the limb bud to form the muscles. As in other regions, connective tissue dictates the pattern of muscle formation, and this tissue is derived from somatic mesoderm, which also gives rise to the bones of the limb. 62 With elongation and rotation of the limb buds, the muscle tissue splits into flexor and extensor components Although muscles of the limbs are segmental initially, with time they fuse and are then composed of tissue derived from several segments. 63 The upper limb buds lie opposite the lower five cervical and upper two thoracic segments, and the lower limb buds lie opposite the lower four lumbar and upper two sacral segments As soon as the buds form, ventral primary rami from the appropriate spinal nerves penetrate into the mesenchyme On the other hand, the cardiac and smooth muscles developed from the splanchnic mesoderm respectively 64  Summary Of Muscular Development Skeletal muscle is derived from the myotome regions of somites. Some head and neck muscles are derived from pharyngeal arch mesenchyme. Tongue musculature from the occipital somites The limb muscles develop from myoblasts surrounding bones in the limbs. Cardiac muscle and most smooth muscle are derived from splanchnic mesoderm. Absence or variation of some muscles is common and is usually of little consequence 65 Clinical correlates Poland anomaly; failure of pectoralis major muscles to develop 66 QUESTION 1 Which one of the following group of muscles are derivatives from epaxial division of myotomes? 1. Muscles of back 2. Muscles of limbs 3. Muscles of viscera 4. Cardiac muscles 67  Which one of the following bones ossifies by intramembranous ossification? 1. Vertebra 2. Humerus 3. Ribs 4. Mandible 68  Regarding the ossification of long bones, which one of the following statements is correct? 1. Primary ossific centre appears after birth. 2. Secondary ossific centre leads into ossification of diaphysis. 3. Long bones ossify by intramembranous ossification. 4. When epiphysis unites with diaphysis, growth of bone stops. 69  Which one of the following is the result of rotation of upper limb? 1. The tibia becomes lateral. 2. The flexor muscles become posterior. 3. The ulna becomes medial. 4. The preaxial digit becomes medial. 70