Limb Development

Question 0

What are the three degrees of asymmetry of limb development? How do these occur?

Answer 0

Proximo-distal axis: base of limb to tips of digits

-sculpting of limbs forms digits

Dorsal-ventral axis: back of hand/top of foot to palm of hand/sole of foot

• dorsal ectoderm and ventral ectoderm influence underlying tissue

Anterio-posterior axis: thumb to little finger (1st digits -> 5th digit)
(hands not superimposable mirror images)

• rotation of limbs as they elongate (upper limb rotates laterally and lower limb rotates medially so that thumb is lateral and big toe is medial)
• zone of polarising activity

Question 1

What is a limb bud? Where and when do they appear? What are they derived from?

Answer 1

LIMB BUD = core of proliferating mesenchymal cells with ectoderm covering (cuboidal epithelium)

Appear on ventero-lateral body wall at end of 4th week

Extend ventrally at first (by proliferating mesenchyme)

Limb skeleton formed from mesenchyme of somatic layer of lateral plate mesoderm

Musculature of limbs formed from myotome of somites

Question 2

What is the apical ectoderm ridge? What is its function?

Answer 2

Thickened ectoderm at apex of limb bud

Drives limb elongation until paddles appear and regress

Diffusion limited signalling molecules induce underlying mesenchyme to remain undifferentiated (but still proliferate)

Question 3

What is the zone of polarising activity?

Answer 3

Signalling centre located at posterior base of limb bud which generates anterio-posterior asymmetry

Controls patterning & maintains the apical ectoderm ridge

Question 4

How do the digits of the limbs form?

Answer 4

Digital rays (mesenchyme condensations which form the cartilaginous model of digital bones) present

Regression and apoptosis of apical ectoderm ridge and underlying tissue in between the digital rays (sculpting)

Apical ectoderm ridge maintained over digital rays

Question 5

What are some examples of limb defects?

Answer 5

SYNDACTYLY = fusion of digits (connective tissue or bones)

POLYDACTYLY = extra digits (recessive)

AMELIA = complete absence of a limb

MEROMELIA = partial absence of one or more limb structures
e.g. thalidomide causes phocomelia (limb bud elongation prevented)

Question 6

Outline the stages in limb ossification.

Answer 6

Lateral plate somatic mesoderm condenses & differentiates

Cartilage model forms

Endochondral ossification

Question 7

Outline the stages of the development of musculature of limbs.

Answer 7

Myogenic precursors migrate into limbs from somite (bringing innervation with it)

Forms two muscle masses around skeletal elements

• ventral (flexor)
• dorsal (extensor)

Individual muscles then split from common masses

Question 8

What are the anterior and posterior flexor and extensor compartments located?

Answer 8

ANTERIOR:
Upper limb: flexor compartment (medial & lateral cord branches)
Lower limb: extensor compartment (posterior cord)

POSTERIOR:
Upper limb: extensor compartment (medial & lateral cord branches)
Lower limb: flexor compartment (posterior cord)

Question 9

What is the structural defect underlying congenital hip dislocation (congenital hip dysplasia)? Why is it associated with breech presentation?

Answer 9

Underdevelopment of acetabulum and head of femur

Breech presentation places pressure on developing hip joint

Question 10

What happens if the apical ectoderm ridge is disrupted? How can this happen?

Answer 10

FGF signalling disrupted -> arrested limb development

• interference affecting blood vessels of the AER
• inhibited NK-KB (forms the AER)