10. embryology of limbs and clinical relevance

Question 1

which mesoderm do limbs arise from?

Answer 1

paraxial somites:

• dermatome: connective tissue of dermis
• myotome: limb muscles

lateral plate:

• bone of upper and lower limb
• blood vessels
• connective tissue (except for dermis)

sensory nerve elements from neural crest

Question 2

when do limb buds appear

when does initial growth and patterning occur

Answer 2

4 weeks (bones and basic structures established by 8 weeks)

4-8 weeks

Question 3

what is the most common birth defect

Answer 3

limb defects- complexity

Question 4

what iniates limb outgrowth from the proximal to distal

what is it dependent on

Answer 4

• initiated by apical ectodermal ridge (AER) at tip of limb buds
• process dependent on FGF fibroblast growth factor signalling from AER, disruption causes arrested limb development
• HOX genes specifies each element (what bone)
• disruption causes loss of specifc limbs

Question 5

Dorso-ventral patterning

Answer 5

ventral (BMPs and engrailed-1) and dorsal (Wnt7) signalling factors are antagonistic and sets up AER

disruption of D-V will affect P-D as well

specifies dorsal surface (extensors) and ventral (flexors)

Question 6

anterior-posterior patterning

Answer 6

anterior is towards the head here

• established by zone of polarising activity on posterior side of limb (little finger side)
• Shh sonic hedgehog signalling from ZPA signals posterior elements

Question 7

what is ZPA essential for except for posterior elements

Answer 7

maintaing AER

disruption leads to dysregulation of limb growth

upregulation- too long

lost- too short limbs

Question 8

are posterior or anterior elements formed first?

Answer 8

posterior formed first

therefore disruption of AP patterning growth can result in loss of anterior elements

Question 9

how are digit rays separated

what is this dependent on

Answer 9

tissue undergo apoptosis

dependent on BMP signalling in interdigital tissue under influence of Shh from ZPA

Question 10

which mechanism is the development of bones

Answer 10

endochondral ossification

• mesenchyme forms chondrocytes
• chondrocytes lay down model of bone
• blood vessels invade, osteoblasts localise and proliferate at epiphyses (ends)
• chondryocytes near shaft (diaphysis) undergo hypertrophy, calcified and undergo apoptosis
• growth of long bones continue into adulthood- maintained by FGF signalling of chondrocytes in growth plates

Question 11

how many growth plates to long and small bones have

Answer 11

long have two

smaller (phalange) have one at tip

Question 12

where do vertebral and rib bones arise from

Answer 12

sclerotome of paraxial mesoderm

Question 13

how is myotome further divided

Answer 13

primaxial: adjacent to neural tube, affected by signalling factor from neural tube- muscle precursors with limited migratory potential

• epiaxial: muscles of back (dorsal rami)
• hypaxial: muscles of body wall (ventral rami)
  
  • strap, intercosals, neck, proximal limb girdle

abaxial myotome: ventrolateral myoblasts, responds to signals from adjacent lateral plate mesoderm and ectoderm to give rise to migatory population

• muscle precursors that go into body wall and limbs

Question 14

rotation of limb

Answer 14

in lower limb there is permanent pronation twisting the leg

Question 15

amelia

meromelia

phocomelia

Answer 15

absence of entire limb (early loss FGF)

absent of part of limb (later or partial loss of FGF)

short, poorly formed limb (partial loss of FGF, Hox)

Question 16

adactyle

ectrodactyl

polydactyl

syndatyl

Answer 16

absence of digits (later loss of FGF)

lobster claw (missing middle digit) FGF

extra digits (upregulation Shh)

fusion of digits (BMP, Shh disruption)