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
