Mesoderm - Musculoskeletal

Previously on mesoderm: Gastrulation and Embryonic Folding > 2a. Mesoderm and Ectoderm

Limb formation

Paraxial mesoderm forms somites, which are the source of muscles and vertebrae. By week 3, there are 40 pairs of somites.

Functional parts of somites:
Sclerotome: Ventral and medial cells migrating towards the notochord produce vertebrae and ribs at each level.
Dermatome: Dorsal lateral cells migrate to form the dermis of the skin.
Myotome: The dorsal epimere forms the deep back muscles called the erector spinae while the ventral hypomere forms the skeletal muscles of the limbs/abdomen/thoracic wall.

Limb buds

Form from the somatic lateral plate mesoderm while muscle progenitors migrate from the somitic myotome and then into the limb buds. Muscle progenitors form the ventral and dorsal muscle masses.

Mesoderm progenitors → Mono-nucleated myoblasts → multi-nucleated myotube

Clinical pearls

Muscular dystrophy (MD)

X-linked recessive disorder (more common in males). Caused by a defect in the DMD gene which produces Dystrophin.

Dystrophin: Links actin filaments to the extracellular matrix and is required for muscle cell interaction.

• Duchenne Muscular Dystrophy (DMD): Frame shift mutation causing proximal muscle weakness, also affecting the respiratory and and cardiac muscles.
• Becker Muscular Dystrophy (BMD): In-frame mutation which causes partial loss of the Dystrophin protein. More mild phenotype.

Bone development

Types of bone formation

• Endochondral Ossification: Cartilage model forms first, then gets ossified into bone. Bones of the axial skeleton including the vertebrae, ribs, sternum, cranial base, and limbs
• Intramembranous Ossification: Bone forms directly from mesenchyme or neural crest cells. Bones of the face and cranial vault

Long bone formation (Endochondral Ossification)

Epiphysis: Compartment of cartilage growth from progenitor cells that consist of layers of resting chondrocytes
Diaphysis: Compartment of proliferating chondrocytes made of 3 layers

• Proliferating chondrocytes
• Pre-hypertrophic chondrocytes
• Hypertrophic chondrocytes (surrounded by calcified matrix)

Formation steps

1. Vascularization of the hypertrophic region allows for invasion by osteoblasts. These secrete collagen to form primary spongiosa
2. Primary spongiosa becomes the primary ossification center, forming a trabecular network of bone
3. Grows as two epiphyses move in opposite directions by proliferating chondrocytes
4. Bone collar forms around diaphysis
5. Growth plates form at the base of the epiphysis and the proliferating chondrocytes of the diaphysis

Neural crest cell bone formation (Intramembranous Ossification)

1. Mesenchyme condenses into sheets
2. Osteoblasts from vasculature become trapped in the sheet and secrete collagen
3. Mineralization from osteoblasts for trabeculae form spongy bone
4. Spongy bone is filled in by continuous mineralization forming compact bone

Joint types

Fibrous: Mesenchyme between bones differentiate into dense fibrous tissue (e.g. Structure between cranial plates)
Cartilaginous: Mesenchyme differentiates into fibrous/cartilaginous tissue (e.g. Pubic symphysis, costochondral joints (sternum to rib connection))
Synovial: Mesenchyme peripheral to two bones condense into capsular and ligament tissue, then the central mesenchyme undergoes apoptosis leaving a fluid filled synovial region. A synovial membrane forms on the bone surfaces (e.g. knee joint)

Thoracic muscle development

By week 7-8, thoracic muscles develop. They are derived from myotome which has a dorsal epimers (erector spine muscles) and ventral/lateral hypomeres (transversospinalis, hypaxial, and rectus abdominus muscles).

Rib cage development

Week 5: Costal processes (from sclerotomes) elongate along body wall
Week 7: First 7 ribs connect ventrally and cranially to mesenchymal condensates

The xiphoid process does not ossify until birth. The 5 ribs caudal to the sternum (false ribs) do not fuse.