Limb development Flashcards
Limb bud development
precursors to limbs, extend out of somites, develop at end of week 4
Embryology phases of limb development
Week 4 (D 25-27): upper limb buds form, (D 27-29): lower limb buds form.
Week 5: paddle shaped hands and legs
Week 6 and 7: digital rays start to form
Week 8: programmed cell death to remove webbing
Hox genes
determine limb position, includes FGF10, WNT3, FGF8
FGF10
FGF10 restricted to mesenchymal cells of lateral mesoderm –> forms limb buds
FGF10 stimulates WNT3 expression in ectoderm (forms limb buds)
FGF10 induces FGF8 expression in ectoderm (sustains production of FGF10 - positive feedback)
Mesenchyme
derives from mesoderm
loose, connective tissue
- involved in origin, development and differentiation of structures during embryonic development
T-box genes
influence identity of limbs
Tbx5 - forelimb (no gene no forelimb)
Tbx4 and Pitx1 - hindlimb
Tbx2 & Tbx3 - both
Proximo-distal axis signalling centre
AER (apical ectodermal ridge)
= ridge of cells which goes around dorso-ventral axis of limb
when AER is removed, only proximal structures form, the more time exposed to AER, the more distal structures
Proximo-distal molecular signal
FGF8
expressed in AER
allows limb bud to proliferate by keeping limb mesenchyme cells in a mitotically active state
(stimulates FGF10 production)
Anterior-posterior axis signalling centre
ZPA (zone of polarising activity) - found on posterior margin of limb
allows for specification of fingers/thumb by creating a gradient
adding another ZPA on anterior side of limb causes mirror digits to form
Anterior-posterior axis molecular signal
SHH (sonic hedgehog) - creates gradient across limb (ie expressed in different conc. across limb)
expressed in ZPA
allows specification of fingers/thumb
Dorso-ventral axis signalling centre
Dorsal ectoderm (for back of hand) Ventral ectoderm (for palm)
Dorso-ventral axis molecular signal
WNT7a - controls differentiation of dorsal (back of hand) - if removed, 2 palms
En-1 - controls differentiation of ventral (palm) - if removed, 2 back of hands
Programmed cell death in limb development
creates shape of hands - prevents webbing
occurs during week 8 embryonic development
BMP (bone morphogenic proteins) involved in process
BMP
Bone morphogenic protein
controls programmed cell death - removal of protein causes webbing of fingers and toes
Growth of bones
Mesenchyme condenses into cartilage (starting wk 5)
Ossification (laying down bone tissue) then occurs in long bone shafts and at end of bones
A cartilage growth plate remains to allow further growth - full ossification occurs by age 18-20
Development of vasculature
endothelial precursor cells come together to form single cell layered tubes with lumen - which develop into blood vessels
VEGF (vascular endothelial growth factor) is involved
Development of nerves
spinal nerves migrate/grow into limb - eventually innervate dermatomes
Development of musculature
muscle precursors migrate from somite (initially no muscle precursors in limb)
Lbx1 gene required for correct migration (when removed, no muscle mass developed)
somite
bilateral blocks of mesoderm which run from head to tail of embryo
AER stands for
apical ectodermal ridge
ZPA stands for
zone of polarising activity
Effect of thalidomide
(was prescribed for morning sickness)
when taken between day 20-36 -> limb abnormalities
causes over exposure to FGF8 in AER -> creates distal structures, and misses proximal structures
DDH - developmental dysplasia of hip
hip joint ligaments are loose, femoral head not stable in socket
can be caused by mum’s hormones which cause ligament relaxation (for birth)
treated with a brace - holds hip in position until ligaments shrink
Growth of long bones
- initially comprised of hyaline cartilage
- primary centre of ossification starts (centrally)
- secondary centre of ossification (at ends of long bone)
