Development Of Limbs

Question 1

When do the limb buds appear?

Answer 1

Towards the end of the 4th week

Question 2

Do the lower and upper limbs develop simultaneously?

Answer 2

Lower limb development lags (by 2 days)

Question 3

What is a limb bud?

Answer 3

Core of proliferating mesenchymal cells with an ectoderm covering that emerge from the trunk of the embryo

Question 4

How does the limb bud elongate?

Answer 4

Proliferation of mesenchymal core

Question 5

What is the AER?

Answer 5

Apical ectodermal ridge (thickened ectoderm at the apex of the limb?

Question 6

What are the 3 spatial axes in limb development?

Answer 6

1. Shoulder to fingertips
   Proximal – distal axis
2. Palmar surface to dorsal surface
   Dorsal – ventral axis
3. Side – to – side
   Anterior – posterior axis

Question 7

What controls the anterior to posterior axis?

Answer 7

Zone of polarising activity (ZPA)

Question 8

What controls the proximal to distal axis?

Answer 8

Apical ectodermal ridge (AER)

Question 9

What controls the dorsal to ventral axis?

Answer 9

Ectoderm

Question 10

Describe the importance of the apical ectodermal ridge

Answer 10

• Critical for limb bud outgrowth - cells in the ridge are different
• Orchestrates limb development proximal to distal
• Final stage is appearance of paddles (as they flatten)
• Then AER regresses

Question 11

How does the AER orchestrate limb development?

Answer 11

• AER releases signals to tell mesenchyme to remain undifferentiated
• Signals are diffusion limited
• Proximal mesenchyme begins to differentiate into constituent tissues
• Finally, induces development of digits

Question 12

What is the ZPA?

Answer 12

Zone of polarising activity = signalling centre located at the posterior base of the limb bud that contributes to the generation of asymmetry in the limbs

Question 13

What are digital rays?

Answer 13

Mesenchyme condensations within plates that are cartilaginous models of the digital bones

Question 14

How are the digits in the hand and foot formed?

Answer 14

• AER breaks up and its only maintained over the tips of the digital rays
• Interdigital spaces are sculpted by apoptosis

Question 15

What is syndactyly

Answer 15

Fusion of the digits, may involve just CT (e.g. Rosebud hand) or bones may be fused

Question 16

What is polydactyly?

Answer 16

Extra digits, genetic recessive trait

Question 17

What is Amelia?

Answer 17

Complete absence of a limb

Question 18

What is meromelia?

Answer 18

Partial absence of one or more limbs

Question 19

What is phocomelia?

Answer 19

Hand and feet are attached directly to the trunk

Question 20

What causes malformation?

Answer 20

Intrinsic error in coordination of morphogenesis i.e. Something wrong in the signalling mechanisms due to mutation error

Question 21

What is amniotic band constriction?

Answer 21

Congenital disorder caused by entrapment of normally formed foetal parts caused by fibrous amniotic bands while in utero (constriction bands). Leads to deformation.

Question 22

How does thalidomide disrupt morphogenesis?

Answer 22

Disrupts the AER, stops the elongation of limb buds

Question 23

Which external agents can disrupt morphogenesis?

Answer 23

E.g. Thalidomide and TORCH infections

TORCH, which includes Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes infections, are some of the most common infections associated with congenital anomalies.

Question 24

How do the limb buds become innervated?

Answer 24

• Upper limb bud appears opposite the caudal cervical spinal segments
• Lower limb opposite lumbar & sacral spinal segments
• Spinal nerves enter the limb bud early in its development

Question 25

How do bones and muscle form in the newly developed limb buds?

Answer 25

• Mesenchymal differentiation creates a cartilage model
• Myogenic precursors migrate into limbs from somites
• Come together to form two common muscle masses around the newly formed skeletal elements
  1. Ventral = flexor
  2. Dorsal = extensor
• Individual muscles then split from common masses

Question 26

How do the limbs rotate?

Answer 26

• Limbs extend ventrally at first 
• But, as they elongate, they rotate 
• Upper limb: laterally
– thumb lateral 
• Lower limb: medially
– big toe medial

Question 27

Describe the position of the embryo before and after limb rotation

Answer 27

Before

• thumbs up
• elbows out
• soles facing
• knees out

After

• thumbs out
• elbows down
• soles down
• knees up