Session 1

Question 1

When do limb buds appear in limb development of the embryo?

Answer 1

Towards the end of the 4th week - not essential like CNS

Lower limb lags 2 days behind upper limb

Question 2

How does the limb bud develop?

Answer 2

Core of proliferating mesenchymal (flexible) cells with an ectoderm covering
Elongation of limb bud is through proliferation of mesenchyme core
Thickened ectoderm at apex of limb - AER found there

Question 3

What are the 3 axes of limb development?

Answer 3

Shoulder to fingertips (proximal-distal)
Palmar to dorsal (dorsal-ventral)
Side to side (anterior-posterior)

Question 4

What are the controllers of axial specification?

Answer 4

AER - apical ectodermal ridge
Ectoderm
ZPA - zone of polarising activity

Question 5

What is the AER and it’s role in axial specification?

Answer 5

Used for proximal-distal axis
critical for limb bud outgrowth
final stage is appearance of paddles then AER regresses
AER exerts an inductive influence on the direct underlying mesenchyme - remains undifferentiated
proximal mesenchyme starts to differentiate into constituent tissues
AER induces development of digits within hand/foot plates

Question 6

Which axis does the ectoderm influence in terms of axial specification?

Answer 6

Dorsal to ventral

Question 7

What is the role of the ZPA in axial specification?

Answer 7

Anterior to posterior axis
generation of asymmetry in the limbs
controls both patterning and maintains AER
Hand and foot plates form by digital rays (cartilaginous models) and apoptosis between digits
AER breaks up and is only maintained at ends of digital rays
interdigital spaces are shaped via programmed cell death

Question 8

Define syndactyly?

Answer 8

Fusion of digits - may involve just connective tissue or bones may be fused

Question 9

Define polydactyly?

Answer 9

Extra digits - recessive trait

Question 10

Define amelia?

Answer 10

Complete absence of a limb

Question 11

Define meromelia?

Answer 11

Partial absence of one or more limb structures

Question 12

Define phocomelia?

Answer 12

Limbs attached close to trunk

Question 13

What can cause morphogenesis?

Answer 13

• malformation (intrinsic error in coordination of morphogenesis)
• deformation (constriction bands - entrapment of parts of embryo in fibrous bands in utero)
• disruption (external agent - thalidomide/TORCH)

Question 14

How are the upper and lower limb buds innervated?

Answer 14

Upper -> appears opposite the caudal/cervical spinal segments
Lower -> opposite lumbar/sacral segments
spinal nerves enter the limb bud early in its development

Question 15

How do somites become the individual muscles?

Answer 15

Myogenic precursors migrate into limbs from somites
Coalesce into 2 common muscle masses around the newly formed skeletal elements
Individual muscles then split from common masses

Question 16

How do the limbs rotate in the uterus?

Answer 16

Limbs extend ventrally at first - as they elongate they rotate
Upper limb rotates laterally (thumbs up/elbows out -> thumbs out/elbows down)
Lower limb rotates medially (soles facing/knees out -> soles down/knees up)