1. Development of the Musculoskeletal System

2. Objectives At the end of this unit, the student will be able to:
Discuss a timeline of normal development of the musculoskeletal system
Discuss embryological development of bone, disc, muscle, tendon, joint, ligament and articular cartilage.

3. Embryonic Development

4. Notochord Development
Solid cord of mesoderm cells
Formed by the 18th day
Midline, in cranio-caudal axis of the embryo
First sign of skeletal formation
Signals by secreting specialized proteins
Signals overlying ectoderm to form the neural tube
Eventually becomes the nucleus propulsus in the adult vertebrae

5. Germ Layer Development
Day 20: paraxial mesoderms form somites
Begins in cervical region, spread cranially and caudally
Cervical is most advanced part of body.
Three pairs formed per day until 44 pairs develop by week 5
Some will later disappear

6. Somites Somite pairs migrate Cellular pairs
Ventromedial becomes Sclerotome (BONE)
Dorsolateral becomes Dermomyotome
Dermis, Dermatome
Myoblasts, Myotome

7. Somites, early on, become associated with a particular spinal nerve.
When many of the somite cells migrate to new locations in the embryo, they retain this neural link.
Basis for:
referred pain
patterns of cutaneous innervation
nerve supply to muscles
 Axial structures - somites are arranged in pairs alongside the neural tube(light orange) and notochord (blue). Each somite is composed of a dermatome (light purple), myotome (light brown), and sclerotome (dark yellow). The ectoderm lies above and the endoderm below.

8. 4 weeks Major changes in body of embryo
Two pharyngeal arches are visible and two develop
Mandibular arch (first) gives rise to the lower jaw, extension of this gives rise to the upper jaw
Second arch is the hyoid arch
Upper limb buds are recognizable
Pouches for arms
UE forms before LE

9. 5th week Enlargement of head caused by brain development
Articular Cartilage Development
Carnegie Development do not correspond to time, but rather a stage. Do Not Need to Know

10. 6th week
Upper limbs begin to show differentiation into the elbows and large handplates develop
Primorida of the digits develop within the handplates
Beginning of the development of the lower limbs
Trunk and neck begin to straighten
One of the most important times in Musculoskeletal development

11. 6th Week= Vertebrae Development
6th week: chondrification centers appear in each mesenchymal vertebra
Centers in each centrum fuse to form a cartilaginous centrum
Centers in neural arches fuse with each other and cartilaginous centrum and spinous processes, transverse processes develop

12. Each centrum develops from two adjacent sclerotomes
6th week
Intervertebral Disks develop from densely arranged cells which migrate cranially
Remainder of densely packed cells fuse with loose cells to from a mesenchymal centrum. (primordium of vertebral body)
Each centrum develops from two adjacent sclerotomes
Neural tube(light orange)
Notochord (blue)=Nuclueos Pulpuses
Dermaome (light purple)=Vertebra
Myotome (light brown)
Sclerotome (dark yellow).

13. 7th week Limbs undergo change=enlogation
Notches appear between the digits
By end of the week, ossification of the bones in the upper limb has begun
Clavicle one of the first

14. 8th week Digits of the hand are separated but still webbed.
Notches visible between digital rays of the feet
All digits have lengthened and are completely separated
Ossification begins in the femur

15. 9-12 weeks Head is half the length of the body
9 weeks: legs are short, get longer but not to the full extent as at birth, arms are almost their normal length
Primary ossification centers appear in skeleton by end of 12 weeks

16. Specific Tissue Formation
Cartilage
Bone
Vertebrae
Sternum
Ribs
Muscle
Tendon
Joints
Ligaments
Capsule

17. Development of Axial Skeleton
During fourth week
Mesenchymal cells from the sclerotomes are around the notochord, neural tube and in body wall
Sclerotome: loosely arranged cells cranially, densely packed cells caudally

18. 4th week
Notochord degenerates and disappears in areas that are surrounded by the developing vertebral bodies
Above the vertebral bodies, notochord develops into the nucleus pulposus
Snell, R

19. Development of Bone and Cartilage
Mesoderm gives rise to mesenchyme: meshwork of loosely organized embryonic connective tissue
Bones appear as condensations of mesenchymal cells to form a bone model

20. Mesenchymal Bone Formation
Intramembranous ossification
Occurs in mesenchyme that has formed a sheath, becomes highly vascularized
Develops into osteoblasts which deposit osteoid
Snell R. Clinical Embryology for
Medical Students, 2nd ed ,
Little Brown and Co. Boston, MA

21. Process of Bone Formation
Osteoid is cell matrix, deposited by the mesenchyme cells.
Calcium phosphate attaches to the osteoid tissue and traps the osteoblasts within. These cells then become osteocytes.
No pattern develops at first, later organize into lamellae which develop around blood vessels. Osteons (Haversian system)

22. Mesenchyme also develop into bone marrow in this region
Osteoblasts at periphery of developing bone, lay down the lamella, forms plates of compact bone with spongy bone in between
Between spongy environment is region of osteoclastic activity (bone resorption)
Mesenchyme also develop into bone marrow in this region
Snell, R

23. Cartilage Model of Bone Formation
Endochondral Ossification
Primary Center of Ossification
Give the initial length to bone
Secondary Centers of Ossification
Growth plates
Junqueira LC, Carneiro J.

24. Primary Ossification Center
Appears in diaphysis
Chondrocytes increase in size by mitosis, align in rows, enlarge to increase length and diameter
Chondrocytes then die, matrix calcifies and forms a honeycomb appearance
Thin layer of bone deposited under perichondrium which becomes periosteum
Process moves toward the epiphyses

25. At Birth: diaphyses are largely ossified
Epiphyses are still cartilagenous
Secondary ossification centers occur within a few years after birth
Junqueira and Carneiro

26. Summary of Bone Growth
-Hyaline Cartilage start in long shaft are the primary centers
-Secondary centers remain open after birth, while primary close before birth

27. Vertebral Ossification
Ossification of vertebrae begins during embryonic period and ends by age 25
Ossification within neural arches by eighth week
Birth: each vertebrae has three bony parts connected by cartilage
Fuse within first 3-5 years
Sometimes the vertebrae will fuse together.
Snell, R

28. 6th week
Snell, R

29. Arches unite first in lumbar region and progress cranially
Vertebral arch articulates with the centrum at cartilaginous neurocentral joints. These joints permit the vertebral arches growth as the spinal cord enlarges
Five secondary ossification centers appear after puberty – ossify by age 25:
Tip of spinous process
Tip of each transverse process
Superior and inferior vertebral end plates

30. Exceptions to typical vertebral ossification
C1 vertebrae
C2 vertebrae
C7 vertebrae
All lumbar, sacral and coccyx vertebrae
Typical:
7 cervical vertebrae
12 thoracic
5 lumbar
5 sacral
Sometimes L5 fuses to the sacrum (sacralization)
Sometimes S1 doesn’t fuse (lumbarization)

31. Development of the Disc
4th week of gestation:
Mesenchyme cells form the annulus fibrosus
Notochord forms the nucleus pulposus
Sclerotome cells migrate medially to surround the notochord
Notochord becomes encased in a continuous cylinder of sclerotomic mesenchyme
Caudal half of each sclerotome fused with cephalic half of the next scelrotome to form the mesenchymal vertebral body

32. Mesenchymal condensations forms the annulus fibrosus (light band)
5-6 weeks gestation: mesnechymal tissue surrounding notochord begins to segment
Mesenchymal condensations forms the annulus fibrosus (light band)
Non condensed mesenchyme forms the vertebral bodies (dark band)
Ghosh P: The Biology of the Intervertebral
Disc, Vol. I, CRC Press, 1988

33. Notochord enlarges between vertebral bodies, forms nucleus propulsus
Notochord disappears in areas where vertebrae are developing

34. Development of Ribs
Ribs develop from mesenchymal costal processes of thoracic vertebrae
Cartilaginous during embryonic period
Ossify during fetal period
Seven pairs true ribs
Five pairs of false ribs
Two pair of floating ribs

35. Development of Sternum
Pair of sternal bars develop ventrolaterally in body wall
Condrification occurs in bars as they move medially
Fuse craniocaudally to from cartilaginous models of manubrium, sternum and xiphoid process
Centers of ossification appear craniocaudally in sternum before birth except for xiphoid process which occurs during childhood

36. Development of Limbs
Fifth Week: condensations of mesenchyme appear as limb buds
Mesenchymal bone models in limbs chondrify during the sixth week and form hyaline cartilage bone models
Clavicle develops first then pectoral girdle and upper limb bones then pelvic girdle and lower limb bones

37. Ossification begins by 8th week and occurs in primary ossification centers
12th week, all long bones have primary ossification centers
Clavicles begin to ossify before any other bone in the body, then the femurs
Secondary ossification centers occurs in utero, first in the knee, most appear after birth

38. Limbs then rotate in opposite directions and to different degrees
Early 7th week: limbs extend ventrally. Flexor aspect of limbs are ventral and extensors are dorsal.
UE rotate Externally
LE rotate Internally
Limbs then rotate in opposite directions and to different degrees
Upper limbs rotate laterally through 90 dg
Elbows face posterior
Flexors of elbow are anterior
Lower limbs rotate medially through almost 90 dg
Knees face anterior
Extensors of knee are anterior

39. Embryological Development of Joints
Develop during the sixth week with the appearance of the interzonal mesenchyme.
By the end of week eight, they resemble adult joints.
Layer of synovium separates from the joint spaces

40. Fibrous Joint Development
Dense fibrous tissue develops from the interzonal mesenchyme creating the fibrous joints like the cranial sutures.

41. Cartilaginous Joint Development
Interzonal mesenchyme develops into either hyaline cartilage (chostochondral joints) or fibrocartilage (pubic symphysis, clavicle)
Starts week 6 continues into week 8

42. Synovial Joint Development
Interzonal mesenchyme differentiates into (week 7-8):
Peripherally, it forms the capsular and other ligaments
Centrally it disappears and resulting space becomes the joint cavity or synovial cavity
When it lines the joint capsule and articular surfaces, it becomes the synovial membrane

43. Development of Skeletal Muscle
Derived from the myotome regions of somites
First indication of myogenesis is the elongation of the nuclei and cell bodies of the mesenchymal cells which differentiate into myoblasts.
When start to see striation then it is differeante.

44. The primordial muscle cells fuse to form elongated, multinuclear, cylindrical tubes or myotubes.
Muscle growth in the fetus then occurs with ongoing fusion of myoblasts and myotubes.

45. At the time of the fusion myofilaments appear in the cytoplasm of the myotubes
Most skeletal muscle is developed before birth
All developed by age 1, muscles increase in length and width as the skeleton grows.

46. Embryological Development of Tendon
Embryologically, tendon develops from the mesoderm tissue
Develops at a similar time as ligaments and muscle
Initially consists of tenoblasts and type I collagen

47. Upper limb tendons develop before lower limb tendons
Extensor muscles of lower limb don’t fully develop until after birth
Interaction occurs between the tendon cells and muscle cells to coordinate correct insertion of each tendon to its appropriate muscle (Jozsa, Kannus, 1997)

48. Development of Ligament: EX: Anterior Cruciate Ligament
Weeks 9-10
Fibroblasts align between femoral and tibial attachment sites
Collagen fibrils are deposited between cells, parallel to the longitudinal axis of the ligament
As cells deposit more and more collagen, bundles of matrix push cells apart forming a mature ligament with a low density of cells and a higher collagen content

49. References
Moore KL, Persaud TVN. The Developing Human. Clinically Oriented Embryology, 8th ed. Saunders Elsevier, Philadelphia PA, 2008.
Cech DJ, Martin S. Functional Movement Development Across the Life Span, 2nd ed. New York, W.B. Saunders
Whitaker R. Embryology Lectures downloaded from , Podcast accessed on April 30, 2011.