Prenatal limb development

Question 1

When do limb buds appear and which appear 1st?

Answer 1

End of 4th week.

Lower limb development lags about 2 days behind upper limb.

Question 2

What do limb buds consist of?

Answer 2

Core of proliferating mesenchymal cells covered with a layer of ectoderm.

Question 3

What is present at the apex of the limb bud?

Answer 3

Apical ectodermal ridge (AER) = thickened ectoderm

Question 4

How do limb buds elongate?

Answer 4

Proliferation of mesenchyme core.

Question 5

What are the 3 spatial axes in limb development and what are these controlled by?

Answer 5

1. Proximal-distal axis (shoulder to fingertips)
   
   • Apical Ectodermal Ridge (AER)
2. Dorsal-ventral axis (palmar surface to dorsal surface)
   
   • Ectoderm
3. Anterior-posterior axis (little finger to thumb)
   
   • Zone of Polarising Activity (ZPA)

Question 6

What are the functions of the AER?

Answer 6

1. Encourages limb bud outgrowth
2. Mediates proximal to distal axis

AER secretes signals to prevent cellular differentiation and promote division. As signals are diffusion-limited, immediately underlying mesenchyme remains undifferentiated whilst proximal mesenchyme differentiates into constituent tissues (e.g. cartilage).

Question 7

What are the functions of the ZPA?

Answer 7

1. Anterior-posterior axis determination (limb asymmetry)

2. Maintains AER

Question 8

What is the ZPA?

Answer 8

Signalling center located at the posterior base of the limb bud.

Question 9

Describe the formation of hand and foot plates, and the role of the AER in this.

Answer 9

1. Appearance of AER paddles - slight flaring of distal end - once maximal limb length is reached.
2. Formation of digital rays - mesenchyme condensations within plates giving rise to cartilaginous models of the digital bones.
3. Regression of AER, maintained only over the tips of the digital rays.
4. Apoptosis via PCD of tissue in interdigital spaces.

Question 10

Describe the process of limb compartmentalisation and muscle formation.

Answer 10

1. Ossification of long bones from primary centres of ossification in cartlaginous template - create dorsal and ventral compartments.
2. Myogenic precursors (myoblasts) migrate into limbs from somites and coalesce into 2 common muscle masses in each compartment.
3. Individual muscles then split from common masses.

Question 11

Which limb compartments contain the flexor and extensor muscles on formation?

Answer 11

Ventral = flexor
Dorsal = extensor

Question 12

How do the upper limbs rotate during development? How does this change the position of the thumbs, elbows and extensor muscles?

Answer 12

Upper limbs rotate laterally through 90 degrees on its longitudinal axis.

• Thumbs up to thumbs out
• Elbows out to elbows down
• Extensor muscles come to lie on lateral and posterior aspect of limb

Question 13

How do the lower limbs rotate during development? How does this change the position of the soles, knees and extensor muscles?

Answer 13

Lower limbs rotate medially through almost 90 degrees.

• Soles facing to soles pointing down
• Knees out to knees up (anteriorly)
• Extensor muscles come to lie on anterior aspect of lower limb

Question 14

Opposite which spinal segments do the upper and lower limb buds appear?

Answer 14

Upper limb buds appear opposite the caudal cervical spinal segments.
Lower limb buds appear opposite lumbar and sacral spinal segments.