Limb Development

Question 1

When does limb development begin and how?

Answer 1

end of week 4

• somatic lateral plate mesoderm activates and limb buds form
• upper limbs - day 24

lowe limbs - days 25-26

Question 2

What are the different parts of limb development?

Answer 2

1. Bone
2. Muscle
3. Nerve
4. Blood Supply

Question 3

How does limb budding occur?

From what layers?

Via what genes?

Answer 3

• somatic lateral plate mesoderm buds out with a thick layer of ectoderm around it
• upper bud at caudal/cervical level
• lower bud at lumbosacral level
• Hox genes regulate patterning

Question 4

What is the name of the thick layer at the apex of each limb bud?

What is it, what does it do and via what factors?

Answer 4

Apical Ectodermal Ridge

• a thick epithelial structure
• promotes outgrowth of mesenchyme into limb bud via FGF

Question 5

What forms at the posterior portion of the limb bud?

What activates it?

What does it do and via what gene?

Answer 5

Zone of Polarizing Activity

• posterior aggregation of mesenchymal cells
• activated by FGF from AER
• organizes dorsal-ventral-ness of limb via **Sonic **hedgehog gene

Question 6

Explain hand/foot and digit development.

Answer 6

• **Hand/foot plates **develop from distal mesenchyme (end week 6)
• Digital rays form from condensation of plates
• Phalanges begin to form from AER of each ray
• **Notches **form in mesenchyme btwn rays
• Apoptosis via BMPs forms separate digits (end week 8)

Question 7

Explain bone development in limbs.

Answer 7

• Mesenchymal models of bones form (week 5)
• **Chondrification centers **appear + limb skeleton is totally cartilaginous by end week 6
• **Osteogenesis **begins in middle of cart. models (week 7)
• **Primary **Ossification Centers **in all bones by end week 12
• **Carpals **don’t develop til postnatal

Question 8

Explain muscle development in limbs.

Answer 8

• Dermomyotomal somite cells migrate into buds and form myoblasts
• Myoblasts aggregate to form single muscle mass
• Separation of muscle mass into dorsal/ventral extensor/flexor

Question 9

Explain limb rotation.

Answer 9

• Upper Limbs - rotate laterally 90 degrees, elbows point back, extensors posterolateral
• Lower Limbs - rotate medially almost 90 degrees, knees forward, extensors anterior
• thus radius/tibia and ulna/fibula are homologous

Question 10

Explain innervation of limbs.

Answer 10

• Motor axons from spinal cord enter limb buds (5th week)
• **Sensory axons **enter after and use motors for guidance
• Neural crest cells surround axons as neurolemma and myelin

Question 11

What is the name for the area of skin supplied by a single spinal nerve + ganglion?

Answer 11

dermatome

Question 12

What is the name for an area of skin supplied by a single peripheral nerve?

Answer 12

cutaneous nerve area

Question 13

Explain development of limb blood supply.

Answer 13

• **dorsal intersegmental artery **branches supply limb buds w/ capillary network in mesenchyme
• primary axial arteries drain into peripheral marginal sinus
• peripheral veins drain sinus blood
• **angiogenesis **changes vascular pattern during development
• **brachial artery **and common interosseous artery forms from primary axial artery
• **deep artery of thigh + Ant/Post Tibial A. **is leg equivalent of primary axial