Development of Limbs

Question 1

Which limbs develop first?

When do Limb Buds start to develop?

When do Digits start to develop?

When do the primary ossificaiton centers develop?

Which direction does limb development proceed?

Answer 1

Upper Limbs before Lower Limbs (Blood Shunted Cephalically)

Week 4

Week 8

Week 12

Proximal to Distal

Question 2

Limb Cartilage and Connective Tissue are formed from what layer?

Limb Muscle is formed from what layer?

What is released and then subsequently stimulated?

What is then produced in response to reciprocally stimulate the Limb-Forming Mesoderm?

Answer 2

Somatic Layer Lateral Plate Mesoderm

Somites from Paraxial Mesoderm (Hypomere)

FGF-10 released –> stimulates Surface Ectoderm to form Apical Ectodermal Ridge (Thickening of Surface Ectoderm)

FGF-8 and FGF-4 released to stimulate Limb-Forming Mesoderm

Question 3

Proximodistal Development

What do the Stylopod, Zeugopod, and Autopod give rise to?

Answer 3

Stylopod: Humerus & Femur

Zeugopod: Radius/Ulna & Tibia/Fibula

Autopod: Carpals/Metacarpals/Digits & Tarsals/Metatarsals/Digits

Question 4

What is developed in the following weeks:

Week 4

Week 5

Week 6

Week 7

Week 8

Answer 4

• 4
  
  • Limb Buds
• 5
  
  • Hand and Foot plates (Hand before Foot)
  • Chondrification centers appear
• 6
  
  • Digital Rays of Hands
  • Entire limb skeleton is cartilaginous
• 7
  
  • Digital Rays of Feet
  • Osteogenesis of long bones
• 8
  
  • Separate digits formed (Apoptosis - BMP)

Question 5

Limb Musculature

Which Spinal Region Myotomes do the limbs develop?

Limb muscles are derived from what area of cells of the somites?

Motor axons enter the limb buds during which week?

Sensory axons follow what structure and use them for guidance?

Neural Crest cells become what cell type responsible for myelination?

Answer 5

Arms/Hands: Cervical Myotomes

Legs/Feet: Lumbar Myotomes

Dorsolateral Cells

Week 5

Sensory axons follow Motor axons

Schwann Cells

Question 6

Limb Rotation

Which direction do the limbs grow/rotate during the following weeks?

5

6

7

8

Answer 6

Week 5: Limbs point Laterally and Caudally

Week 6: Limbs bend Anteriorly

Week 7: Limbs rotate 90 degrees (Laterally in UE & Medially in LE)

Week 8: Torsion of lower Limbs

Question 7

Describe the Blood Supply of the Limbs (UE and LE)

Answer 7

• UE:
  
  • Dorsal Aorta –> Intersegmental A. –> Primary Axial A. –> Brachial A. and Common Interosseous A.
• LE:
  
  • Dorsal Aorta –> Intersegmental A. –> Primary Axial A. –> Deep A. of Thigh and Posterior Tibial A.

Question 8

Club Foot (Talipes Equinovarus) - Most Common MSK Defect

What is the anatomical appearance?

How is it treated?

More common in who?

Answer 8

Sole of foot turned medially and foot is inverted

All anatomical structures present so treated with casting or taping

Males

Question 9

Developmental Hip Dysplasia

What is it caused by?

Who is it more common with?

Answer 9

Under development of the acetabulum of hip bone

Generalized joint laxity

Females

Question 10

Positioning of the limbs along the craniocaudal axis is regulated by what along the axis?

Answer 10

HOX Genes

Question 11

Proximo-Distal Growth Patterning is dependent on what?

What regulates the types and shapes of the bones?

What proceeds from proximal to distal?

Answer 11

FGF signaling

HOX Genes

Apical Ectodermal Ridge (AER) proceeds proximal to distal

Question 12

Dorso-Ventral Patterning differentiates limbs into what surfaces and what types of muscles?

Ventral Surface mainained by what? Dorsal Surface maintained by what?

Answer 12

Dorsal surface (extensors) and Ventral surface (flexors)

Ventral (BMPs) & Dorsal (Wnt7)

Question 13

Anterior Posterior Patterning is established by what on the posterior side of the limb (little finger/ulna side)?

Signaling of what from ZPA signals posterior elements?

Loss of ZPA results in what?

Upregulation of ZPA results in what?

Duplication of ZPA results in what?

Posterior elements formed prior to anterior, so disruption of A-P patterning/growth can result in what?

Answer 13

Zone of Polarizing Activity (ZPA)

Shh and Retinoic Acid

Loss of Posterior Elements

Additional Posterior Elements (Polydactyly)

Duplication of Posterior Elements (Polydactyly)

Loss of anterior elements

Question 14

Birth Defects

Polydactyly

Brachydactyly

Syndactyly

Phocomelia - Meromelia vs Amelia

Ectrodactyly

Arthrogryposis (Congenital Joint Contractures)

Answer 14

• Polydactylyl:
  
  • More than five fingers or toes on hand or foot.
  • Upregulation or Duplication of ZPA
• Brachydactyly
  
  • Shortening of the fingers and toes
  • Autopod - FGF-4, 8, 10 Regulation (weeks 6-8)
• Syndactyly
  
  • Some or all of the fingers or toes wholly/partly united
  • BMP Downregulation (week 8)
• Phocomelia
  
  • Amelia (Wk 3-4) & Meromelia (Wk 3-5)
  • Lacking limbs / Hands or Feet are attached close to the trunk & underdeveloped
  • Side effect of thalidomide taken during early pregnancy.
• Ectrodactyly (Split Hand/Foot)
  
  • Absence of 1+ central digits of hand/foot
  • Hands (Wk. 6) & Feet (Wk. 7)
• Arthrogryposis (Congenital Joint Contractures)
  
  • Usually involves multiple joints