Musculoskeletal development

Question 1

What is the embryonic precursor of skeletal muscle?

Answer 1

paraxial mesoderm

Trunk/limbs= Somatic Mesoderm (dermomyotome portion of the somite)

Head/neck= Head Mesoderm

Question 2

What is the embryonic precursor of cardiac muscle?

Answer 2

splanchnic mesoderm

Question 3

What is the embryonic precursor of smooth muscle?

Answer 3

splanchnic mesoderm and local mesenchyme

Question 4

What embryonic cells develop into connective tissue?

Answer 4

Mesenchymal

**Note: Bone and Cartilage are considered specialized types of connective tissue

Question 5

What is the primaxial muscle domain?

Answer 5

Myoblasts from the dorsomedial dermomyotome form the primaxial muscle domain

**Becomes muscles that attach to scleratome-derived bones (spine and ribs)

Question 6

What is the abaxial muscle domain?

Answer 6

Myoblasts from the dorsolateral dermomyotome form the abaxial muscle domain

**Becomes muscles of the ventrolateral abdominal wall and limbs

Question 7

What is Dermamyotome?

Answer 7

A transient plate structure containing cells that have multiple developmental fates (part of the somite under Wnt signaling where cells maintain their epithelial characteristics)

**Note: looser cells in the ventromedial aspect of the somite form the scleratome

Question 8

How do mature skeletal muscle fibers develop?

Answer 8

1. myogenic cells (“pre-myoblasts”) express myogenic regulatory factors
2. myogenic cells proliferate/migrate and become postmitotic myoblasts
3. myoblasts then fuse into multinucleated myotubules
4. myotubules become mature skeletal muscle fibers (myofibers)

Question 9

What embryonic precursor cells form satellite cells?

Answer 9

A portion of the dermomyotome forms an “under layer”, undergoes EMT (epithelial to mesenchymal transformation) and will form Satellite Cells

Question 10

What are some proposed strategies for the formation of individual named skeletal muscles from skeletal muscle masses?

Answer 10

• Change in fiber direction of different layers [e.g. abdominal wall and intercostal muscles]
• Fusion of adjacent myotome levels [most muscles]
  
  • This is the basis for innervation by multiple spinal cord levels
• Longitudinal splitting into parts [e.g. strap and trapezius/sternomastoid muscles]
• Tangential splitting into layers [e.g. abdominal wall and intercostal muscles]
• Atrophy (partial or complete) [e.g. fronto-occipitalis muscle]
• Migration to regions remote from origin [e.g. superficial back and serratus muscles]

Question 11

What muscles are innervated by Dorsal Primary Rami of spinal nerves?

Answer 11

Muscles forming from the dorsal epaxial portion of the myotome (e.g. the intrinsic muscles of the back) receive motor innervation from the Dorsal Primary Rami of spina nerves

**mostly primaxial muscles

Question 12

What muscles are innervated by Ventral Primary Rami of spinal nerves?

Answer 12

Muscles originating from the ventral hypaxial portion of the dermatome (e.g. ventrolateral body wall and limb muscles) receive their motor innervation from the Ventral Primary Rami of spinal nerves.

**mostly abaxial muscles (some primaxial)

Question 13

At what stage are muscles innervated in development?

Answer 13

Muscles are innervated at the myotome stage as pre-muscle masses (some then migrate and take their innervation with them)

Question 14

When in development have muscle groups formed and are located near their final destination?

Answer 14

8 weeks

Question 15

Describe Congenital Muscular Torticollis

Answer 15

• characterized by a fixed rotation and tilting of the head to one side
• common and may be recognized at or sometime after birth
• can occur in the absence of trauma suggesting a primary defect with the sternocleidomastoid (SCM) muscle, or because of insufficient space for the fetus in the uterus

Question 16

Describe Duchenne Muscular Dystrophy

Answer 16

• MD= a family of genetic diseases exhibiting progressive weakness and deterioration of skeletal muscle (without CNS or peripheral nervous pathology)
• onset occurs in infancy to late adult
• Duchenne’s= skeletal muscle myocytes lack dystrophin, a membrane associated actin binding glycoprotein that stabilizes the cell membrane
• muscle fibers are more susceptible to damage when physically stressed (myofibers eventually replaced with fatty and fibrous tissue over time)

Question 17

What is Prune belly syndrome?

Answer 17

characterized by three defects:

1) absence of abdominal muscles,
2) undescended testicles
3) bladder and urinary tract anomalies

Question 18

What is Poland sequence?

Answer 18

• characterized by absence of the pectoralis major (usually the sternocostal head) and also the pectoralis minor muscles
• as a result, the nipple on that side is displaced laterally or may be missing, associated breast tissue is either hypoplastic or missing, and there is a deficiency of subcutaneous fat and axillary hair

Question 19

From what embryonic tissue is skeletal tissue derived?

Answer 19

**Skeletal Tissue Forming Mesenchyme (STFM)

• in the trunk
  
  • paraxial mesoderm (Scleratome tissue of somites)
  • somatic mesoderm
• in the head
  
  • neural crest extomesenchyme
  • head mesoderm

Question 20

What are the master genes for bone and cartilage formation?

Answer 20

• RunX2= osteoblast specific transcription factor (bone forming)
  
  • RunX2/CBFA1 null mutant mouse has no bones; small limbs and a partially calcified cartilagenous skeleton
• Sox 9= chondroblast specific transcription factor (cartilage forming)

Question 21

What are the steps of development of supporting tissues?

Answer 21

1. STFM often migrates or is displaced from its site of origin
2. STFM forms a Preskeletal Condensation of epithelial-like cells
3. Specific transcription factors (Sox9/RunX2) mediate the differentiation of the preskeletal mesenchyme
4. Differentiation of STFM is also influenced by signals from adjacent epithelium (e.g. surface ectoderm, neural tube or the notochord)

Question 22

Contrast endochondrial and intramembranous ossification

Answer 22

• endochondrial
  
  • cartilage model of bone forms first (Sox9 signaling)
  • some chondrocytes undergo hypertrophy and secrete type X collagen and bone specific proteins (Ihh/RunX2 signaling)
  • bone replaces cartilage (RunX2 signaling)
• intramembranous
  
  • bone directly forms from mesenchyme (RunX2 signaling)
  • e.g. flat bones of skull/face

Question 23

What is an ossification center?

Answer 23

• The areas of a bone primordia in which the ossification process begins (intramembranous and endochondral)
• Primary Ossification Center
  
  • the initial ossification center to form in a developing bone (some bones have only one, but many have multiple)
  • center of flat bones/diaphysis of long bones
• Secondary Ossification Centers
  
  • centers of bone formation appearing in the prenatal, the postnatal or the postpuberal period
  • close in 20s/30s (epiphyseal carilage amount helpful in determining the “bone age” of a child)

Question 24

Describe generalized skeletal tissue dysplasias

Answer 24

• may affect all or part of the skeleton
• often affect growth (may result in short or tall stature)
• often a component of the ECM is defective
• often there is a recognized genetic component

Question 25

What are Mucopolysaccharidoses?

Answer 25

* a family of metabolic diseases that affect bone formation resulting in _dwarfism and bone irregularities_ * defects in **synthesis, storage, or transport of a particular lysosomal enzyme** (results in the accumulation of substrate)

Question 26

Describe Marfan syndrome

Answer 26

* patients have spider-like, _elongated digits_, and may also have aortic aneurysms, eye and spine abnormalities and joint hypermobility * autosomal dominant * caused by a defect in _Fibrillin production_, a component of the ECM

Question 27

Describe how hyperpituitarism affects bone growth

Answer 27

* causes overproduction of Growth Hormone usually due to a tumor of pituitary gland tissue * if this occurs prior to epiphyseal plate closure, it results in **_gigantism_** (very rare) * if it occurs after epiphyseal closure, it results in _Acromegaly,_ a condition where there is disproportionate enlargement of face, hands and feet \*\*low amounts of GH lead to **pituitary infantilism (a type of dwarfism)**

Question 28

Describe how hypothyroidism affects bone growth

Answer 28

* patients are characterized as a **Pituitary Dwarf (cretinism)** * experience mental retardation as well as skeletal and ear anomalies * bone age is younger (more epiphyseal tissue) than it should be for their chronological age

Question 29

Describe Achondroplasia

Answer 29

* mutation of the **FIbroblast Growth Factor Receptor 3 (FGFR-3) gene** which interferes with cartilage formation -\> **_endochondral ossification problem_** * autosomal dominant * most common cause of short stature (dwarfism) * _interference with epiphyseal plate development_ results in disproportionally shortened limbs (mainly the proximal segment). \*\*normal sized trunk * short fingers and an accentuated lordosis * normal intelligence

Question 30

Describe osteopetrosis

Answer 30

* "marble bone disease"; failure of osteoclasts to resorb bone tissue * bone remodeling and modeling are affected, resulting in a skeleton that is _fragile even though bone mass is increased_ * can be congenital, intermediate form diagnosed in childhood, or adult onset

Question 31

Describe Osteogenesis Imperfecta

Answer 31

* brittle bones caused by a defect in expression of the _Type I Collagen_ gene * affects the skeleton (multiple fractures), eyes (blue sclera), ears, joints, spine and teeth * can observe bowing of humerus