Movement lecture 1: Limb development

Question 1

When does limb development take place?

Answer 1

Mid-late embryonic phase, weeks 4-8.

Question 2

What is visible at the end of week 4?

Answer 2

Limb buds are visible as outpouchings from the ventrolateral body wall.

Question 3

What does core limb bud tissue consist of?

Answer 3

Derived from lateral plate mesoderm covered by a layer of ectoderm.

Question 4

What does the limb bud mesoderm core differentiate into?

Answer 4

Mesenchyme

Question 5

What will the mesenchyme form?

Answer 5

Bones and connective tissue.

Question 6

What germ layer is the skeletal muscle of the limbs derived from?

Answer 6

Paraxial mesoderm.

Question 7

What happens to the paraxial mesoderm either side of the neural tube and how is this relevant to limb development?

Answer 7

Develops into somites. These will migrate into limb buds and form skeletal muscle.

Question 8

Describe somite differetiation in the limb buds.

Answer 8

1. Divide into a ventral part called the sclerotome, which forms the vertebral column.
2. The dorsolateral part forms a dermomyotome which divides into a dermatome and a myotome.
3. The dermatome gives rise to the dermis of the skin and the myotome gives rise to skeletal muscles.

Question 9

What two components does the myotome differentiate into?

Answer 9

Dorsal epimere and ventral hypomere.

Question 10

What develops from the epimere?

Answer 10

Back muscles which are innervated by the dorsal rami of spinal nerves.

Question 11

What develops from the hypomere?

Answer 11

Muscles of thoracic and abdominal walls and muscles of limbs which are innervated by the ventral rami of spinal nerves.

Question 12

Does limb skeletal muscle form from hypomere or epimere?

Answer 12

Hypomere - region adjacent to the level of the developing upper (C5-8) and lower (L3-5) limb buds.

Question 13

How is the hypomere divided?

Answer 13

Into the posterior and anterior condensation.

Question 14

Which muscles are derived from the posterior condesation?

Answer 14

Extensors and supinators of the upper limbs.

Extensors and abductors of lower limbs.

Question 15

What is the origin of the nerve supply to the limbs?

Answer 15

Ventral primary rami.

Question 16

What is the origin of the nerve supply to the upper limb?

Answer 16

Brachial plexus C5-T1

Question 17

What is the origin of the nerve supply to the lower limb?

Answer 17

Lumbosacral plexus

Question 18

Why do anterior and posterior compartments of limbs have different nerve supplies?

Answer 18

Each spinal nerve migrates into the limb bud with the developing musculature as anterior and posterior branches.

Question 19

Between what weeks does limb rotation occur?

Answer 19

6-8

Question 20

Describe the rotation of the upper limbs.

Answer 20

Upper limbs rotate 90° laterally so flexors lie anteriorly.

Question 21

Describe the rotation of the lower limbs.

Answer 21

Lower limbs rotate 90° medially so flexors lie posteriorly.

Question 22

What are the axes of the limb?

Answer 22

Proximodistal – from the shoulder/hip to the hand/foot

Craniocaudal – the thumb is most cranial digit and the little finger is most caudal

Dorsoventral – the palm of the hand and sole of the foot are ventral and the knuckle side of the hand/foot are dorsal

Question 23

What is secreted by the lateral plate mesoderm forming the mesenchymal core of the limb bud?

Answer 23

Fibroblast growth factor (Fgf 10).

Question 24

What is the function of the apical ectodermal ridge?

Answer 24

Expresses fibroblastic growth factors -Fgf 4 and 8. These cause rapid proliferation of mesenchymal cells underlying the AER – the progress zone. The progress zone maintains proximodistal outgrowth of the limb.

Question 25

What is the effect of early removal of the AER?

Answer 25

The limb is extremely forshortened.

Question 26

What is the effect of late removal of the AER?

Answer 26

The limb is partially forshortened.

Question 27

What is the effect of implanting Fgf-soaked beads?

Answer 27

Supernumerary limbs at the site of implantation.

Question 28

How is dorsoventral patterning controlled?

Answer 28

The dorsal ectoderm expresses Wnt7 whereas the ventral ectoderm expresses Engrailed-1 which inhibits Wnt7

Question 29

What happens to Wnt7 knockout mice?

Answer 29

They develop foot pads on the dorsal and ventral surface.

Question 30

How is the craniocaudal axis determined?

Answer 30

The craniocaudal axis is determined by a small region of mesenchyme in the caudal part of the limb bud – the zone of polarising activity (ZPA) - where sonic hedgehog (Shh) is expressed.
Shh diffuses from the ZPA in a cranial direction.

Question 31

How does sonic hedgehog protein work?

Answer 31

High concentration of Shh induces formation of caudal structures e.g. little finger whereas low concentration induces formation of cranial structures e.g. thumb.

Question 32

How are digits formed?

Answer 32

Fingers and toes are formed by programmed cell death (apoptosis) in the AER. This splits the AER into 5 parts which continue to grow to form fingers.

Question 33

Define amelia.

Answer 33

Complete absence of a limb e.g. early loss of Fgf signalling.

Question 34

Define meromelia.

Answer 34

Partial absence of a limb e.g. later or partial loss of Fgf signalling.

Question 35

Define phocomelia

Answer 35

Digits develop prematurely. Proximal elements of limb absent e.g. flipper limb. Can be due to genetic factors or teratogen e.g. Thalidomide inhibits Fgf 10 and 8 expression.

Question 36

Define syndactyly.

Answer 36

Fused digits. Failure of apoptosis.

Question 37

Define polydactyly.

Answer 37

Extra digits. inappropriate/ectopic shh expression.