S1) Embryology of the Musculoskeletal System

Question 1

When do the limb buds appear?

Answer 1

The limb buds first appear as small projections on the lateral body wall during the fourth week of development

Question 2

Describe the structure of the limb buds

Answer 2

• The buds consist of a mass of mesenchyme covered by a layer of ectoderm
• At the tip of the bud the ectodermal cells divide to form an apical ectodermal ridge

Question 3

Which limb develops first?

Answer 3

Upper limb buds develops a few days before the lower limb buds

Question 4

What drives limb elongation?

Answer 4

Proliferation of mesenchyme (induced by AER)

Question 5

As the limbs elongate, they rotate.

Describe the rotation of the upper and lower limbs

Answer 5

• The upper limb rotates laterally through 90° so extensor muscles lie on the posterior aspects of the limb
• The lower limb rotates medially through almost 90° so extensor muscles lie on the anterior aspects of the limb

Question 6

Identify the three spatial axes in limb development

Answer 6

• Proximal-distal axis

- Dorsal-ventral axis

- Anterior-posterior axis

Question 7

Identify the controllers of axial specification in limb development

Answer 7

- Zone of Polarising Activity controls anterior-posterior axis

- Apical Ectodermal Ridge controls proximal-distal axis

- Ectoderm controls dorsal-ventral axis

Question 8

What does the AER do?

Answer 8

AER lies immediately above the mesenchyme and orchestrates limb development from proximal to distal then regresses

Question 9

Describe how the proximal-distal axis is generated by the AER

Answer 9

• AER exerts an inductive influence on mesenchyme so it remains undifferentiated
• Proximal mesenchyme begins to differentiate into constituent tissues
• AER induces development of the digits within the hand/foot plates

Question 10

What is the Zone of Polarising Activity and what does it do?

Answer 10

• ZPA is a signalling centre located at the posterior base of the limb bud
• It controls maintains the AER and generates the asymmetry of the limbs (anterior – posterior axis determination)

Question 11

What are the digital rays?

Answer 11

• Mesenchyme condensations within plates
• Cartilaginous models of the digital bones

Question 12

Describe how apoptosis sculpts the digits of the upper and lower limbs

Answer 12

• AER breaks up and is maintained only over the tips of the digital rays
• Interdigital spaces are progressively sculpted by programmed cell death

Question 13

Describe the innervation of the upper and lower limb buds

Answer 13

• Upper limb buds appear opposite the caudal & cervical spinal segments
• Lower limb buds appear opposite the lumbar & sacral spinal segments

Question 14

Describe the development of limb compartments

Answer 14

• Myogenic precursors migrate into limbs from somites (body segments)
• They coalesce into 2 common muscle masses around the newly formed skeletal elements

Question 15

Identify the two compartments in the limbs

Answer 15

• Flexor compartment (ventral)
• Extensor compartment (dorsal)

Question 16

Identify and describe 3 underlying problems in morphogenesis

Answer 16

• Malformation – intrinsic error in coordination of morphogenesis
• Deformation – constriction bands
• Disruption – external agent e.g. thalidomide

Question 17

What is syndactyly?

Answer 17

Syndactyly is the fusion of digits (connective tissue / bones)

Question 18

What is polydactyly?

Answer 18

Polydactyly is an autosomal recessive trait resulting in extra digits

Question 19

What is amelia?

Answer 19

Amelia is the complete absence of a limb

Question 20

What is meromelia?

Answer 20

Meromelia is the partial absence of one or more limb structures