UNSW Embryology

DEVELOPMENT OF THE MUSCULOSKELETAL SYSTEMS - text only page

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Reading Reading Moore Ch16,17: p370-373, 375-382 Larson Ch11: p281-299

Computer Activities UNSW Embryology: Body Cavities, Musculoskeletal & Limb Development Embryo Images Unit: Systems (Pig Limbs), Human (stage development), Human (body groups 1, 2, 3), Systems (limbbud) C4-E3

Objectives Name the components of a somite and the adult derivatives of each component. Give examples of sites of (a) endochondral and (b) intramembranous ossification and to compare these two processes (consult Histology Manual). Enumerate the general times (a) of formation of primary and (b) of formation of secondary ossification centres, and (c) of fusion of such centres with each other. (Refer to Introductory Anatomy notes). Briefly summarise the development of the limbs. Describe the developmental aberrations responsible for the following malformations: selected growth plate disorders; congenital dislocation of the hip; scoliosis; arthrogryposis; and limb reduction deformities.

Learning activities Identify the component parts of a somite in a 6-7mm pig embryo (from 6mm pig microfiche). List the derivatives of a thoracic somite. Examine slides 9, 10, 12, 56 and 57 and identify the type of ossification that is present or has occurred at various sites in each slide.

Examine in the following slides, the features listed for each slide: 9 hyaline cartilage forming bone by endochondral ossification. Study vertebrae from distal to proximal end of tail. Identify: zone of resting chondrocytes; zone of proliferating chondrocytes, zone of maturing chondrocytes (hypertrophy); zone of calcifying cartilage and developing trabeculae of diaphysis; periosteum; periosteal collar of spongy bone; osteoblasts; osteocytes; osteoclasts. Note also the nucleus pulposus and the formation of intervertebral ligaments between ends of adjacent tail vertebrae. 10 developing bones and synovial joints in rat leg: all features of slide 12; articular hyaline cartilage; synovial membranes. 11 compact bone; marrow cavity. By closing condenser aperture diaphragm, identify Haversian systems (osteons) with concentric lamellae, interstitial lamellae, osteocytes, radial canaliculi. Identify circumferential lamellae under periosteum and endosteum of the shaft. At low magnification, identify Volkmann's canals and Haversian canals. Note radial artefact folds in section. 12 long bone (LS): diaphysis; epiphysis; epiphyseal disc; zones of metaphysis as follows - zone of resting chondrocytes, zone of chondrocyte mitosis, zone of maturing chondrocytes (hypertrophy), zone of calcifying cartilage and developing bony trabeculae of diaphysis; osteoblasts; osteocytes; multinucleated osteoclasts with eosinophilic cytoplasm; bone marrow; periosteum. Hyaline articular cartilage: note absence of perichondrium on articular surface of head of femur. 56A,56 intramembranous ossification in cranial bones dorsal to the developing brain; mesenchymal cells; osteoblasts in rows; osteocytes; osteoclasts; bone trabeculae; blood vessels. Note that the hyaline cartilage near the medial border of the mandible is Meckel's cartilage and does not undergo endochondral ossification in this region. Examine the X-rays provided and determine the approximate age of the subject in each case. 5. List the stages of the two types of ossification processes. 6. Discuss the development of vertebrae. 7 . Discuss the development of joints. 8. Discuss the selected malformations below giving special reference to the developmental aberrations causing the malformations and the consequences of malformations to the individual: growth plate disorders; congenital dislocation of the hip; scoliosis; arthrogryosis; limb reduction deformities.

UNSW Embryology Program Pig Embryo Somites: G5: Tangential section through the rump of the embryo (neural tube cut twice). Young somites containing somitocoeles and consisting of dark, lateral dermomyotomes and more diffuse, medial sclerotomes. Notochord. Amnion and amniotic cavity. D1: Surface bulge of a somite, either side of neural tube. Somite components: dermatome, myotome, sclerotome. Notochord. Paired dorsal aortae, with inferior cardinal veins (lateral). Dorsal root ganglion. Spinal nerve passing between sclerotome and myotome. Dl-D3: Dermatome, myotome, sclerotome. Dorsal root ganglia. Notochord. Note the dorsal segmental branches of the dorsal aortae and the inferior cardinal veins. In the walls of the neural tube, note the alar and basal laminae of cells, sulcus limitans.   Axial Skeleton - Vertebrae: G7: Cervical region: dark masses of dorsal root ganglia. Lumbar region: dorsal aorta with its dorsal segmental arterial branches. Between each dorsal segmental artery is a darker-staining mass of mesenchyme (the dark part of a sclerotome) which is the anlage of the intervertebral disc. The dorsal segmenta lartery itself marks the location of the centre of the light-staining part of the sclerotome, which is the future vertebral body. The dark band dorsal to the sclerotomes is the basal lamina of the wall of the neural tube. G6: Cervical region (neural tube cut very obliquely): note the wavy notochord and thin roof and floor plates. Thoracic region: alternating light and dark parts of the sclerotomes (vertebral bodies and I.V. Discs, respectively). Lumbar region: tiny, dorsal segmental branches of dorsal aorta Each little branch is aligned almost parallel to the cranial border of the next caudal dorsal root ganglion (segmented dark masses). Sacral region: oblique section of neural tube, notochord.   Limbs: D3: Cranial edge of forelimb fold (future shoulder region). Note the superolateral extent of the coelomic serosa with respect to the limb fold. D4,D5: Note axillary fossa appearing on each side and local thickening of the ectoderm in the region of the fossa. Note thinnest ectoderm stretched over heart and neural tube. D6-D7: Limb folds and fossae. Greatest thickening of the ectoderm is at apex of the limb fold: the apical ectodermal ridge. The mesenchyme of the limb is densest under the ectoderm. Note the narrow distance between the ectoderm of the axillary fossa and the serosa of the body cavity. The limb fold has distinct flexor and extensor surfaces: the flexor surface is narrower and has thicker ectoderm. Note blood vessels close to flexor surface E1-E3: Note blood vessels in limb fold mesenchyme, and pale-staining nerves at root of limb (E1). E4: Spinal nerves (part of future brachial plexus) directed towards the flexor side of the limb fold. Note also the section of the lumbosacral region with neural tube and hindlimb bulge. E5-E7: Hindlimb fold. Forelimb fold F1,F2: Caudal limit of forelimb. Broad extensor surface. Dense mesenchyme of hindlimb. Note lumbar somites, somitocoeles. Human Embryo Axial Skeleton D1,D2: Vertebral body (centrum). Head of rib. Lamina of vertebral arch. Transverse processes. Vertebral canal. Spinal cord. Dura. Intervertebral foramen containing dorsal root ganglion (now in a ventral position!). Ribs. Sympathetic ganglia. Costovertebral and costotransverse joints. Note that laminae of the arches have not fused dorsally but are united by a connective tissue membrane (dorsal uniting membrane or ligament) which provides the guide-path for the growth and subsequent fusion of the laminae. The dura constitutes the ventral uniting membrane or ligament. Part of I.V. disc seen in D2. D3: Ganglia in intervertebral foramina. Costovertebral joint. D4: Pedicle of vertebral arch. The dark, fibrous tissue at the anterior margin of the vertebral column is the intervertebral disc (derived from dark part of sclerotome). Note ribs joining the sternum, intercostal muscles and erector spinae group of muscles. E4: Vertebral body with I.V. disc ventrally. Notochord remnant at junction of body and I.V. disc. E6: Next vertebral body (notochord incorporated into cartilage). F1: Mostly I.V. disc with notochord remnant (cf. F2) F2: Transverse abdominal muscle, internal and external oblique abdominal muscle, rectus abdominis muscles. F7,G1: (Lumbar cross-section). Vertebral body and I.V. disc. Psoas major muscle. Erector spinae muscles. Note short laminae of the arches and wide dorsal uniting ligament.   Upper limb (Rows C-D) C5,C6: Scapula. Spine of scapula. Humerus (head). Clavicles. Deltoid muscle. Trapezius muscle. C7: Scapula spine. Deltoid muscle. Trapezius muscle D1,D2: Flexor and extensor muscles of arm. D3: Elbow mesenchyme (elbow flexed) D5: Carpal and metacarpal cartilages. Phalanges. (Note flexed, pronated position of arms). Humerus. Radius.   Lower limb (Row G) G1: Knee mesenchyme G2: Patella. Femur. Flexor and extensor muscles. G4: Knee joint. Tibia and femur. Hip bone: pubis, ischium, ilium, head of femur. Developing acetabulum. Adductor group of muscles. G5: Hip joint. Acetabulum. Head and greater trochanter of femur. Sacro-iliac joint. G6: Heel. Ischium. Sacro-iliac joint. G7: Tarsal cartilages (note inverted position of feet). Heel. Phalangeal cartilages. Human Embryo (selected sections) D4,D6: Dura (ventral uniting ligament). Spinal ganglia. Intervertebral foramen. Ependyma of spinal canal. Ventral horn. Dorsal horn. Anterior spinal artery. Centrum of vertebra. Lamina of arch. Note that the dura invests the spinal ganglion and then dorsally fuses with the perichondrium of the neural arch before continuing to the opposite side as the dorsal uniting ligament (not seen in D6)

Self Assessment Questions 1. List the main steps in the development of a vertebra. 2. What is the cartilage model in bone growth? 3. Compare and contrast endochondral and intramembranous ossification. 4. Describe the main steps in the development of a long bone. 5. What are the derivatives of myotomes and dermatomes? 6. Describe the main events in the development of the limbs. 7. What is an epimere and a hypomere? 8. Describe the biochemical disorders associated with the major growth plate disorders? 9. What are the major causes and consequences of congenital dislocation of the hip and scoliosis?

DEVELOPMENTAL ABNORMALITIES

The "figures" referred to below are on posters in the practical classroom. Clinical Introduction: 1. Normal growth and development of the limb requires (a) normal cell numbers; (b) normal locomotor elements, e.g. bone, joint, muscle; (c) normal blood and nerve supply. 2. Retardation of limb growth is produced by (a) deficient nerve supply; (b) impaired blood supply or (c) systemic abnormalities affecting the growth plate. 3. Increased limb growth is produced by some nerve malformations and by increased blood supply to the growth plate.

I. GROWTH PLATE DISORDERS (a) Hurler's Syndrome (b) Morquios Syndrome (c) Achondroplasia (d) Osteogenesis imperfecta (Fragilitas ossium) (Brittle Bone disease) (e) Marfan's Syndrome   (a) Hurler's Syndrome: Photo GP1 ((a & b) Genetic Mucopolysaccharides) A seemingly normal infant, in a matter of a few years, may be transformed into a mentally retarded, physically deformed, severely handicapped individual. No organ or tissue appears to be spared the inbuilt error of metabolism, which is the accumulation of mucopolysaccharides (chondroitin sulphate B and heparin sulphate). The form inherited as an autosomal recessive is most severe: the sex linked recessive form affects males only and is less severe. Death occurs in childhood or early adult life. The main histological features are the presence of inclusion bodies composed of mucopolysaccharides within cells of the growth plate, the C.N.S. and parenchymal and connective tissue cells.   (b) Morquios Syndrome: Photo GP2   In this disease keratosulphate accumulates in cartilage and cornea. (The patients excrete excessive keratosulphate in the urine - a diagnostic criterion). Severe stunting becomes apparent in the second and third year of life. The joints then become involved and osteoporosis becomes prominent. The cartilage has abnormal chemistry, and the problem is a systemic metabolic disorder.   (c) Achondroplasia: Photo GP3 (An autosomal dominant)   This is a deficiency of endochondral ossification and all growth plates are affected - other forms of cartilage such as articular cartilage and hyaline cartilage are normal. These are the characteristic circus dwarfs, healthy, well muscled, short adults with limbs short relative to the trunk. A major problem in this disease is the failure of the germinal cells of the growth plate to proliferate.There are two possible mechanisms for this disease :- 1. An abnormality of vascular invasion of calcified cartilage leading to an accumulation of uncalcified cartilage. 2. An abnormality of cartilage which precludes calcification.   (d) Osteogenesis imperfecta - Fragilitas ossium. Brittle bone disease (autosomal dominant with variable expressivity). Photo GP4   This is a generalised disorder of connective tissue which has a variable expression. In its most severe form there are brittle bones, lax joints and hypotonic (floppy) muscles. The pathological change underlying this disorder is a failure of collagen production throughout the body. Normally collagen becomes a thicker and stronger fibre as it matures. In osteogenesis imperfecta collagen remains in the form of reticulin. In place of normal compact bone, a course fibrillary type of immature bone is found without haversian systems and with a very irregular distribution of abnormal collagen fibres in the bone. Photo GP5; GP6. Photo 5 shows a typical example of Osteogenesis imperfecta with malformation due multiple fractures and Photo 6 the typical appearance of bone.   (e) Marfan's Syndrome Photo 7 (autosomal dominant)   This is a generalised disorder of the connective tissue of the body with manifestations in the skeleton, eye and vascular system. The individuals are tall and thin and there is an overgrowth of endochondrial ossification. There are also systemic and locomotor disabilities. Aortic incompetence often occurs. There is an abnormality of elastic fibres in this disease but the connections between this and the malfunction of the growth plate is obscure.

II. CONGENITAL DISLOCATION OF THE HIP (C.D.H.)   Introduction (Instability: 1:60 at birth; 1:240 at 1 wk: Dislocation untreated; 1:700).   (a) There is originally a congenital instability of the hip which later dislocates by muscle pulls or gravity if untreated. (b) There is familial predisposition for this problem and female predominance. (c) Growth of the femoral head, acetabulum and innominate bone are delayed until the femoral head fits firmly into the acetabulum.   Mechanisms of Production (a) There is familial displasia of the hip. (b) There is a relationship between placental transmission of material joint softening hormones (e.g. Relaxin) which are inhibited by androgens in the male foetus. When a and b are present there is instability of the hip. (c) Dislocation is produced by the small head slipping out of the shallow acetabulum in the extended position of the hip and is inhibited by the abducted position of the hip.   Treatment Treatment must be instituted early to avoid a growth deformity of the hip. To ensure there is no instability, infants are tested at birth for hip stability and unstable hip children are nursed in the Frog Position (abducted hip posture). Photo CDH1 Pawich Brace Photo CDH2 Frog Plaster   Delay in treatment leads to frank dislocation of the hip (the femoral head comes out of joint), and there is a shallow acetabulum and a small femoral head. See Photo CDH3. If this condition is allowed to occur an operation may be necessary to produce a more horizontal roof to the acetabulum and produce hip stability. See Photo CDH4. Posterior dislocation of the hip produces flexion deformities of the hip with compensatory Lordosis - exaggerated lumbar curvature. See Photo CDH5 (both female). Questions 1. In CDH5 the smaller child on the right shows Trendelenberg's Sign - as she raises her right foot the right side of the pelvis lowers instead of raising. In the normal patient the hip rises when the ipsilateral foot is raised from the ground. What muscle is chiefly responsible for the normal tilting of the hip? 2. What conditions may give rise to Trendelenberg's Sign?

III. ARTHROGRYPOSIS (Multiplex Congenita) Rare Severe cases are characterised by multiple deformities at birth with gross stiffening of joints and hypotonia or wasting of muscles.   Photo AG1. Such a stiff fetus frequently sustains fractures before or during delivery. AG1 has had a fractured right humerus. Photo AG2 shows deformities originally thought to be joints, then joints and muscles then finally innervation was also implicated. Photo AG3 shows normal and abnormal muscles in close proximity. Variations in the degree of severity of joint deformity are expressions of varying degrees of muscular and neurological abnormality.

IV. SYNDACTYLY Fusion of fingers or toes. This may be single or multiple and may affect (i) Skin only (ii) Skin and soft tissues (iii) Skin, soft tissues and bone   See Knock out Mouse Reference The condition is unimportant in toes but disabling in fingers and requires operative separation. This is frequently inherited as an autosomal dominant. Photo

V. SCOLIOSIS This is involved with assymetric growth impairment of the vertebral bodies. There is lateral deviation of the spine with a 3-fold deformity: 1. Lateral flexion 2. Forward flexion 3. Rotation of the vertebral column on the long axis   Photos: Sco 1: Shows Scoliosis Sco 2: Rotational deformity producing rib hump when the child bends Sco 3: X-ray of spine The deformity is compensated by movement of the vertebral column above and below the affected region producing a primary and two secondary curves. This deformity progresses rapidly in adolescence and becomes fixed once bone growth is completed.   Questions Why does the deformity progress rapidly in early adolescence?

VI. CONGENITAL LIMB REDUCTION DEFECTS Thalilomide was the most celebrated limb reducing insult in humans which produced other deformities as well. There was probably a primary neuronal deprivation. There are two elements in the production of limb reduction defects.   (a) Agents - Many substances have been found capable of producing limb reduction defects in experimental animals but few have been related to humans. (b) Mechanisms - Limb reduction defects may be due to loss of blood supply to part of the limb or to defects in innervation at the spinal or cerebral level. Also there are a number of as yet undefined mechanisms involved.   Limb reduction defects may be apical (congenital amputation) or pre- or post-axial (absence of radius and lateral digits; ulnar and medial digits). Photo LRD 1 and 2 shows a limb reduction defect and the accompanying X-ray.   Questions What area is missing in the reduced limb? What will be the relative growth rates of the right and left humeri in this child? Other examples of limb reduction defects are shown by :- Photos: LRD 3:A reduction defect, largely preaxial hemimelia LRD 4: An apical defect LRD 5: A severe apical defect, the lobster claw foot. Question What problems would a patient with the lobster-claw foot defect encounter when walking?

OMIM Database Online Mendelian Inheritence in Man Database. OMIM Internet Search OMIM database with the keyword skmus or the above abnormality names. Note: This database is an external link, not accessible from some computers in the School of Anatomy. A is available for these computers.

Self Assessment Questions (C.V.S.)

References There is also a selected list of Research Articles and Reviews from PubMed related to cardiac development and abnormalities. A Selected List of References from PubMed March 1999 search results for "skmus/review/5year limit" and "Cardiovascular/Development/2year limit" is available for School of Anatomy computers without internet access.

PubMed Database Online Medline Database PubMed- Medline National Library of Medicine (US) search service to access the 9 million citations in MEDLINE and Pre-MEDLINE (with links to participating on-line journals), and other related databases. Internet Search this database or use the form below with the keyword skmus or related topics. You can also restrict to reviews or by date published. Note: This database is an external link, not accessible from some computers in the School of Anatomy. A Selected List of References from March 1999 search results for "" and "" is available for these computers. Search Field: Affiliation All Fields Author Name EC/RN Number Entrez Date Issue Journal Name Language MeSH Major Topic MeSH Terms Page Publication Date Publication Type Subheading Substance Name Text Word Title Word Volume MEDLINE ID PubMed ID Mode: Automatic List Terms PubMed PubMed Search Results Number as of March 1999.

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• Lecture notes from the Anat 3311 1997 Science Embryology course compiled and written by Dr Mark Hill. Some notes derived from historic class notes.
• Note Links to OMIM Entries are copies of originals for computers without internet access. Computers with internet access can directly access the database.

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