Lecture 7- MSK Development

Question 1

When does limb development occur

Answer 1

• week 3-8

Question 2

Stages of development

Answer 2

• Blastocyst: first 2 weeks
• Embryonic: week 3-8
• foetal: week 9+

Question 3

Gestional age vs embryonic age

Answer 3

• Gestional age: time since last menstuation

- Embryonic age: time since fertilisation

Question 4

When do limb buds appear

Answer 4

Week 4

Question 5

When do hand plates and digital rays appear

Answer 5

Weeks 5,6

Question 6

When do webbed digits appear

Answer 6

Weeks 7,8

Question 7

Appearance of

• upper limb buds
• lower limb buds
• joints of hand

Answer 7

• mid 4th week
• 2 days later
• day 47

Question 8

2 specialized structures in the limb buds

Answer 8

• Apical ectodermal ridge: ridge of cells around the dorsoventral axis
• Zone of polarizing activity: group of cells on posterior margin of limb bud

Question 9

Limb positioning controls

Answer 9

• hox genes in embryonic trunk -> FGF10 on lateral plate mesoderm -> Wnt3 in overlying ectoderm -> dorms AER and induces expression of FGF8

FGF8: proliferation of mesenchyme cells
- positive feedback loop

Question 10

Determining the identity of limbs

Answer 10

• Tbx5: forelimb
• TBx4 and Pitx1 hindlimb
• Tbx2/3: both limbs

Question 11

Proximal distal axis of limb

• Signaling center
• molecular signal

Answer 11

• AER

- FGf8

Question 12

Antero-posterior axis of limb bud

• signaling center
• molecular signal

Answer 12

• ZPA

- shh gradient posterior to anterior

Question 13

Dorso-ventral axis of limb bud

• signaling center
• molecular signal

Answer 13

• Dorsal and ventral ectoderm

- Molecular signal: Wnt7a (dorsal), En-1 (ventral)

Question 14

Programmed cell death

Answer 14

• shaping of limb structures

- BMP are involved in this process

Question 15

Bone formation

Answer 15

• mesenchyme initially condences into cartilage

- ossification starts in shafts of long bones and secondary sites at the end of bones

Question 16

Vasculature

Answer 16

First blood vessels formed by vasculogenesis

• vessels form de novo in embryonic mesenchyme
• Endothelial precursor cells form an aggregate and produce a small single-layered endothelial tube with a lumeb
• VEGF involved

Question 17

Nerved

Answer 17

• develop as dermatomes

- first parallel then mixed up

Question 18

Musculature

Answer 18

• muscle precursors migrate frm the somites of the animal into the limb to form muscles
• Lbx1 gene required for migration

Question 19

Syndactyly

Answer 19

Fusion of digits

- BMP or Shh disruption

Question 20

Polydactyly

Answer 20

• extra digits

- Shh disruption

Question 21

Triphalangeal thumb

Answer 21

• shh disruption

Question 22

Amelia

Answer 22

Absence of an entire limb

- early loss of Fgf signalining

Question 23

Meromelia

Answer 23

Absence of part of a limb

Question 24

Adactyly

Answer 24

Absence of digits: late loss of Fgf

Question 25

Thalidomide effects

Answer 25

- loss of immature blood vessel - mesenchymal cells cant proliferate - longer exposure to FGF8 in AER - more distal structures, less proximal structures

Question 26

Developmental displasia of hip

Answer 26

1/1000 - female predominance - first born - increased risk with breech position and big baby TREATMENT: Pavlik harness

Question 27

Perthes disease

Answer 27

- hip of growing children - more common in boys aged 4-10 - disruption of blood supply to part of femoral head - softening and collapse of bone - unknown cause - inflammation, limping - broomstick plasters - good prognosis

Question 28

Club foot (Talipes)

Answer 28

- most common muscoloskeletal defect in children - constriction of feet in breech position -> inturned feet) - males TREATMENT - gradual plastering technique - 95% success rate

Question 29

Toewalking

Answer 29

- walking on toes or ball of fooot - can be habitual/idiopathic TREATMENT - stretching and strengthening

Question 30

Calcaneal apophysitis: Sever's disease

Answer 30

- inflammation of growth plate - heel pain - one or both heal - stress/overuse/obesity/ tight achilles tendon - pain, limping, toewalking TREATMENT - reduce activity, calf stretcking, orthotis, ibuprofen