Embryo - Limb Development

Question 1

What are the Characteristics of the Development of Limbs?

Answer 1

Basics:

• Limb buds = paddle projections
  
  • Ventrolateral body wall
• Upper limb buds first
  
  • 26th -27th day
  • Opposite to C5-T1 spinal segments
    
    • contribute to brachial plexus
• Lower limb buds second
  
  • 2 days later
  • Opposite to L4-S3 spinal segments
    
    • contribute to sacral plexus

Limb buds:

• Mesenchymal core
  
  • derived: somatic layer of lateral plate mesoderm
• Covered by ectoderm

Note:

• Activation of mesenchymal cells in the lateral mesoderm starts off the process of limb development

Question 2

What are the 3 types of Mesoderm? What do Somites give rise to?

Answer 2

Basics:

• Lateral plate mesoderm
  
  • subdivision of the intraembryonic (2nd) mesoderm
  • forms connective tissue of the limbs
• Paraxial Mesoderm
  
  • divdes into 42-44 pairs of somites
• Intermediate mesoderm
  
  • urogenital system

Somites give rise to…

1. Sclerotome
   
   • Vertebrae & ribs
2. Myotome
   
   • Muscle
3. Dermatome
   
   • Connective tissue
     
     • Dermis

Question 3

What is the importance of an Apical Ectodermal Ridge (AER)?

Answer 3

Basics:

• Activation of mesenchyme induces formation of apical ectodermal ridge (AER)
  
  • mesenchyme condenses
    
    • gives rise to skeleton & connective tissue
• Molecular signaling causes formation of AER
  
  • drugs can affect development of the limbs
• AER = start of limb formation​
  
  • loose mesenchyme –> condensed mesenchyme –> cartilage

AER:

• Ectodermal thickening at the apex of each limb bid
• Inductive influence on limb mesenchyme
  
  • stimulates proliferation of mesenchyme
    
    • progress zone
  • growth & development of the limbs
• Interaction btw AER & Mesenchyme = essential for limb dev.

Question 5

How do limbs develop from Week 4 - Week 8?

Answer 5

Week 4

• Limb buds appear

Week 5

• Hand & foot plates formed
  
  • Chondrification centers form

Week 6

• Digital rays appear
• Tissue btw digits = undergo apoptosis
  
  • form notches
  • entire limb = cartilaginous

Week 7

• Upper limbs bend at elbow
• Fingers = short & webbed
  
  • Osteogenesis of long bones = begins via 1° Ossifcation Centers
  • Ossification of the carpal & tarsal bones = after 1st year of birth

Week 8

• Digits are distinct & separate

Question 6

How does Upper and Lower Limb Development Progress from Day 26 - Day 52?

Answer 6

Question 7

What are the Positional Changes of Developing Limbs?

Answer 7

48 Days

• Limbs extend ventrally
• Hand & Foot plates face each other

51 Days

• Upper limbs bend at elbow
• Hands curved over thorax

54 Days

• Soles of feet face medially

56 Days

• Elbows point = caudally
• Knees point = cranially

Question 8

How does Limb Rotation differ from Upper/Lower Limbs?

Answer 8

• Upper Limb
  
  • Rotates 90° laterally
  • Flexors = Anterior
  • Extensors = Posterior
• Lower Limb
  
  • Rotates 90° medially
  • Extensors = Anterior
  • Flexors = Posterior

Question 9

How does Ossification of Appendicular Skeleton Occur?

Answer 9

Basics:

• Bones of the limbs & limb girdles are formed = endochondral ossification (except for the clavicle)
  
  • Mesenchymal cells gives rise to a cartilaginous model –> ossifies

Fetus:

• Diaphysis
  
  • formed by primary ossification center in long bones
  • week 7-8
    
    • Epiphysis/carpus/tarsus = still cartilageninous

After Birth

• Epiphysis
  
  • formed by secondary ossification centers
  • appear during 1st 4 years

Child/Teen/Young Adult

• Epiphyseal plate
  
  • Growth plate btw diaphysis & epiphysis
    
    • addes length to bone
    • persists until done growing

Question 10

What causes Rickets?

Answer 10

• Vitamin D deficiency leads to impaired calcium absorption by the intestine
  
  • calcium deficiency causes disturbance in ossification of epiphyseal plates
    
    • short & deformed limbs

Question 11

What is Achondroplasia?

Answer 11

• Premature fusion of epiphyses (growth plate)
  
  • short stature
  • bowed limbs
  • short trunk
  • enlarged head
• Autosomal dominant
  
  • 1: 15,000

Question 12

What is Syndactyly/Polydactyly?

Answer 12

Syndactyly

• Cutaneous syndactyly
  
  • Webbing of the digits
• Osseous syndactyly
  
  • Fusion of the bones

Polydactyly

• Extra digits
• Can be posterior/anterior
  
  • not in the middle

Question 14

What is Congenital Club Foot?

Answer 14

• Talipes equinovarus
• Foot is turned medially and inverted
  
  • Common anomaly
• Gets fixed on its own as child learns to walk

Question 15

What are the difference between Amelia & Meromelia?

Answer 15

Amelia

• Complete absence of limbs
• Suppression of limb bud dev.
  
  • Week 4

Meromelia

• Partial absence of limbs
• Disturbance of limb development
  
  • Week 5

Question 16

How do Cleft Hand & Cleft Foot Develop?

Answer 16

• Absence of one or more central digits
  
  • Failure of development of one or more digital rays
• Remaining digits are partially or completely fused
  
  • Rare anomaly
  • Lobster‐claw deformities

Question 17

What is Amniotic Band Syndrome?

Answer 17

• Tears in the amnion result in amniotic bands
• May encircle fetal limbs & digits
  
  • Ring constrictions
  • Amputations

Question 18

How do Dermatomes arise?

Answer 18

Basics:

• Motor axons arise from the spinal cord & enter limb bud
  
  • 5th week
• Sensory axons enter limb buds after the motor axons
  
  • Use them for guidance

Dermatomes:

• Neural crest cells
  
  • precursor of schwann cells
  • surround moto/sensory nerve fibers in limbs
  • form the neurolemma & myelin sheaths
• Dermatome = area of skin supplied by 1 single spinal nerve & ganglion

Note:

• Spinal nerves = distributed in segmental bands
• Orderly sequence –> recognized even after growth of limbs

Question 19

How does the Development of Limb Arteries Occur?

Answer 19

• Limb buds supplied by branches of the intersegmental arteries
  
  • Arise from dorsal aorta
  • Form fine capillary network throughout mesenchyme
• Primordial vascular pattern
  
  • Primary axial artery & branches

Question 20

What are Myotomes of Body Somites?

Answer 20

• As long bones form, myoblast aggregate and form a muscle mass in each limb bud
  
  • Muscle mass separates into flexor and extensor compartments

Image:

• Epaxial myotome = intrinscic muscles of the back
• Epaxial division = dorsal