L1 Limb Development

Question 1

During which period of gestation does organogenesis (including limb development) take place?

Answer 1

Until week 8

Question 2

Which part of the trilaminar disc is responsible for forming the limbs?

Answer 2

Intermediate mesoderm: gives rise to cartilage, bone and vasculature

Question 3

The __?__ forms a series of blocks called somits on either side of the neural tube.

Answer 3

paraxial mesoderm

Question 4

What does the ventral part of each somite differentiate into?

Answer 4

Sclerotome - eventually forming the vertebral column

Question 5

What does the dorsal part of each somite differentiate into?

Answer 5

Dermomyotome:

• Dermatome –> dermis of skin
• Myotome –> skeletal muscles

Question 6

The myotome differentiates and forms:

• The __1__ muscles, which are innervated by the dorsal rami of spinal nerves
• The thoracic and __2__ muscles, which are innervated by the ventral rami of spinal nerves

Answer 6

1) back

2) abdominal wall

Question 7

The mesoderm that will form the limb muscles migrates into the limb buds and divides into two parts.

The posterior condensation will eventually form all of the following except one. Which of these answers is INCORRECT?

a) Extensors of the lower limbs
b) Extensors of the upper limbs
c) Adductors of the lower limbs
d) Supinators of the upper limbs

Answer 7

c) Adductors of the lower limbs

The posterior condensation will form the extensors, supinators and abductors

The anterior condensation will form the flexors, pronators and adductors

Question 8

What is the innervation of the limb buds?

Answer 8

The limb buds are innervated by the ventral primary rami of spinal nerves:

• Upper limb: brachial plexus (C5-T1)
• Lower limb: lumbosacral plexus (L4-S3)

Question 9

True or false: the developing upper limbs undergo lateral rotation, while the lower limbs rotate medially

Answer 9

True

Question 10

Which of these relationships represents the craniocaudal axis?

a) Shoulder to hand
b) Thumb to little finger
c) Palmar surface of hand to the dorsum of the hand

Answer 10

b) Thumb to little finger

The thumb is the most cranial digit and the little finger is most caudal.

Question 11

Which of these relationships represents the proximodistal axis?

a) Shoulder to hand
b) Thumb to little finger
c) Palmar surface of hand to the dorsum of the hand

Answer 11

a) Shoulder to hand

The shoulder is more proximal and the hand more distal.

Question 12

Which of these relationships represents the dorsoventral axis?

a) Shoulder to hand
b) Thumb to little finger
c) Palmar surface of hand to the dorsum of the hand

Answer 12

c) Palmar surface of hand to the dorsum of the hand

The palmar surface is ventral and the dorsum is [not surprisingly] dorsal.

Question 13

How do the limbs develop proximodistally?

Answer 13

Mesenchymal core of the limb bud secretes Fibroblast Growth Factor (FGF 10). This induces formation of the Apical Ectodermal Ridge.

The AER expresses FGF 4 and 8, stimulating rapid AER proliferation in the progress zone (immediately underlying the AER). The progress maintains proximodistal outgrowth of the limb.

As the AER moves further from cells, it’s influence decreases and they begin to develop into their permanent structures.

Question 14

What is the result of early removal of the apical ectodermal ridge?

Answer 14

Amelia - failure of distal limb to develop

Question 15

What is the result of removing the AER in the later stages of limb development?

Answer 15

Meromelia - partial distal limb failure, the most distal parts will not develop.

Question 16

How does cleft limb occur?

Answer 16

Failure of the central part of the apical ectodermal ridge

Question 17

The zone of polarising activity is responsible for what part of limb development?

Answer 17

Craniocaudal development of the digits.

The zone of polarising activity lies in the caudal part of the limb bud. The cells in the ZPA express sonic hedgehog gene (SHH). High SHH concentrations induce development of caudal structures (the little finger), while low concentrations induce cranial structures (thumb).

Question 18

What is the result of having an ectopic ZPA?

Answer 18

Polydactyly

Mirror digit sequence: little fingers develop on both the cranial and caudal sides. The other digits develop in order, but in duplicate and in mirror image to each other.

Question 19

How is dorsoventral patterning regulated in the developing limb?

Answer 19

Dorsal ectoderm expresses Wnt7, which activates LMX1 - essential for inducing production of dorsal structures.

The ventral ectoderm expresses Engrailed-1, which inhibits Wnt7. Therefore, LMX1 is not activated in the ventral region.

Question 20

What causes nail-patella syndrome?

Answer 20

Mutation of LMX1b - can affect development of some structures, including the nails, patellae, kidneys and eyes.

Question 21

What process forms the fingers?

Answer 21

Apoptosis

In week 6, the terminal portion of the limb buds flatten to form hand and foot plates. Apoptosis divides the AER into 5 parts which continue to grow to form fingers and toes. Apoptosis continues between the digits resulting in separation.

Question 22

Failure of normal apoptosis during the later stages of limb development results in what abnormality?

Answer 22

Syndactyly (fused digits)

Question 23

What condition results in absence of the proximal elements of the limbs, leaving the person with only the distal elements?

Answer 23

Phocomelia

Can be genetic, but most commonly associated with thalidomide, which inhibits FGF 8 and 10.

Question 24

How is supernumerary limb caused?

Answer 24

Ectopic FGF

Question 25

What causes cleft hand/foot?

Answer 25

Failure of the middle of the AER to form properly

Question 26

What causes syndactyly?

Answer 26

Failure of normal apoptosis

Question 27

What causes polydactyly?

Answer 27

Inappropriate/ectopic SHH expression

Question 28

What causes Nail-Patella Syndrome?

Answer 28

Defect of LMX1b gene