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

Question 21

segmental elements

Answer 21

makes building the body more efficient

Question 22

hox genes

Answer 22

gives location for different segments in the body