Week 2 L3: Embryological development of the limbs

Question 1

When does the limb bud develop?

Answer 1

week 5

Question 2

When do the thumbs and digits form?

Answer 2

week 8

Question 3

Which germ layer forms the limb tissue?

Answer 3

mesoderm –> gives rise to bone, skeletal muscle, some organs and blood vessels

Question 4

Explain the pathway for mesoderm to result in ventral and dorsal myotome

Answer 4

1. Mesoderm forms somites
2. Somites differentiate into the sclerotome and the dermomyotome
3. Sclerotome develops the vertebral column
4. Dermomyotome divides into a dermatome and myotome
5. Dermomyotome forms dermis of the skin
6. Myotome forms ventral and dorsal myotome
7. Ventral myotome forms muscles of the limbs, thoracic and abdominal walls
8. Dorsal myotome forms back muscles

Question 5

What does the mesoderm in the limb buds condense into?

Answer 5

1. Anterior condensation –> flexors of UL and LL

2. Posterior condensation –> extensors of UL and LL

Question 6

Why are the extensors of the UL posterior but the extensors of the LL anterior?

Answer 6

Limb rotation
-UL rotates medially
-LL rotates laterally
explains why the thumb is on the lateral aspect of your hand, and why the thumb is on the medial aspect of your foot

Question 7

What are the 3 axis that the limbs develop along?

Answer 7

1. Proximodistal - lengthens limb
2. Craniocaudal - ‘outwards’
3. Dorsoventral - ‘front to back’

Question 8

What is AER?

Answer 8

Apical ectodermal ridge

Question 9

Which growth factor contributes to lengthening of the limb, or thickening of the AER?

Answer 9

FGF10 (fibroblast growth factor 10)

Question 10

What is the name of the zone that maintains proximodistal outgrowth? (lengthening of limb)

Answer 10

progress zone (PZ)

Question 11

Whta is amelia?

Answer 11

• complete absence of limbs
• early failure of FGF10 signalling
• PZ doesn’t develop

Question 12

what is meromelia?

Answer 12

• partial absence of limbs

- later or partial loss of FGF10 signalling

Question 13

What is Cleft hand/foot?

Answer 13

• failure of the central part of the AER to form

- 3rd digit is missing - lateral digits usually form

Question 14

What would ectopic FGF10 result in?

Answer 14

supernumerary limbs –> if FGF10 is found somewhere it shouldn’t be, a second limb might develop

Question 15

Which region influences craniocaudal folding?

Answer 15

zone of polarising activity (ZPA)

Question 16

What is secreted by ZPA?

Answer 16

Sonic hedgehog hormone

Question 17

Explain how different concentrations of sonic hedgehog result in the fingers looking as they do?

Answer 17

• high concentration of SHH induces development of caudal structures e.g little finger
• low concentration of SHH induces development of cranial structures e.g thumb
• ring, middle and index all look similar because they develop in similar concentrations of SHH

Question 18

Why does polydactyly (extra digits) occur?

Answer 18

inappropriate/ ectopic SHH expression

Question 19

Whta is nail patellar syndrome?

Answer 19

• rare condition affecting the nails, bones, kidneys and eyes
• defect in LMX1B gene
• abnormalities in nails
• small or absent patallae

Question 20

When do hand and foot plates form?

Answer 20

week 6

Question 21

What creates seperation between digits?

Answer 21

apoptosis in AER splits plates into 5 segments

Question 22

What is syndactyly?

Answer 22

• fused digits

- failure of normal apoptosis between developing limbs

Question 23

What are the causes of limb abnormalities?

Answer 23

• Genetics - hereditary or spontaneous mutations
• Drugs - ‘teratogens’
• Environmental toxins/poisons e.g retinoids (roacitane), thalidomide
• Maternal illness
• Amniotic band syndrome - bands of tissue coming around amniotic sac getting wrapped around organs

Question 24

What is phocomelia?

Answer 24

• very rare
• digits develop prematurely
• proximal elements of limbs absent
• most commonly associated with thalidomide

Question 25

Which drug inhibits expression of FGF10 and 8?

Answer 25

thalidomide