Lecture 7- MSK Development Flashcards
When does limb development occur
- week 3-8
Stages of development
- Blastocyst: first 2 weeks
- Embryonic: week 3-8
- foetal: week 9+
Gestional age vs embryonic age
- Gestional age: time since last menstuation
- Embryonic age: time since fertilisation
When do limb buds appear
Week 4
When do hand plates and digital rays appear
Weeks 5,6
When do webbed digits appear
Weeks 7,8
Appearance of
- upper limb buds
- lower limb buds
- joints of hand
- mid 4th week
- 2 days later
- day 47
2 specialized structures in the limb buds
- Apical ectodermal ridge: ridge of cells around the dorsoventral axis
- Zone of polarizing activity: group of cells on posterior margin of limb bud
Limb positioning controls
- 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
Determining the identity of limbs
- Tbx5: forelimb
- TBx4 and Pitx1 hindlimb
- Tbx2/3: both limbs
Proximal distal axis of limb
- Signaling center
- molecular signal
- AER
- FGf8
Antero-posterior axis of limb bud
- signaling center
- molecular signal
- ZPA
- shh gradient posterior to anterior
Dorso-ventral axis of limb bud
- signaling center
- molecular signal
- Dorsal and ventral ectoderm
- Molecular signal: Wnt7a (dorsal), En-1 (ventral)
Programmed cell death
- shaping of limb structures
- BMP are involved in this process
Bone formation
- mesenchyme initially condences into cartilage
- ossification starts in shafts of long bones and secondary sites at the end of bones
Vasculature
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
Nerved
- develop as dermatomes
- first parallel then mixed up
Musculature
- muscle precursors migrate frm the somites of the animal into the limb to form muscles
- Lbx1 gene required for migration
Syndactyly
Fusion of digits
- BMP or Shh disruption
Polydactyly
- extra digits
- Shh disruption
Triphalangeal thumb
- shh disruption
Amelia
Absence of an entire limb
- early loss of Fgf signalining
Meromelia
Absence of part of a limb
Adactyly
Absence of digits: late loss of Fgf
Thalidomide effects
- loss of immature blood vessel
- mesenchymal cells cant proliferate
- longer exposure to FGF8 in AER
- more distal structures, less proximal structures
Developmental displasia of hip
1/1000
- female predominance
- first born
- increased risk with breech position and big baby
TREATMENT: Pavlik harness
Perthes disease
- 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
Club foot (Talipes)
- most common muscoloskeletal defect in children
- constriction of feet in breech position -> inturned feet)
- males
TREATMENT
- gradual plastering technique
- 95% success rate
Toewalking
- walking on toes or ball of fooot
- can be habitual/idiopathic
TREATMENT
- stretching and strengthening
Calcaneal apophysitis: Sever’s disease
- 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
