Limb development

Question 1

Limb bud development

Answer 1

precursors to limbs, extend out of somites, develop at end of week 4

Question 2

Embryology phases of limb development

Answer 2

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

Question 3

Hox genes

Answer 3

determine limb position, includes FGF10, WNT3, FGF8

Question 4

FGF10

Answer 4

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)

Question 5

Mesenchyme

Answer 5

derives from mesoderm
loose, connective tissue
- involved in origin, development and differentiation of structures during embryonic development

Question 6

T-box genes

Answer 6

influence identity of limbs
Tbx5 - forelimb (no gene no forelimb)
Tbx4 and Pitx1 - hindlimb
Tbx2 & Tbx3 - both

Question 7

Proximo-distal axis signalling centre

Answer 7

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

Question 8

Proximo-distal molecular signal

Answer 8

FGF8
expressed in AER
allows limb bud to proliferate by keeping limb mesenchyme cells in a mitotically active state
(stimulates FGF10 production)

Question 9

Anterior-posterior axis signalling centre

Answer 9

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

Question 10

Anterior-posterior axis molecular signal

Answer 10

SHH (sonic hedgehog) - creates gradient across limb (ie expressed in different conc. across limb)

expressed in ZPA

allows specification of fingers/thumb

Question 11

Dorso-ventral axis signalling centre

Answer 11

Dorsal ectoderm (for back of hand)
Ventral ectoderm (for palm)

Question 12

Dorso-ventral axis molecular signal

Answer 12

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

Question 13

Programmed cell death in limb development

Answer 13

creates shape of hands - prevents webbing
occurs during week 8 embryonic development

BMP (bone morphogenic proteins) involved in process

Question 14

BMP

Answer 14

Bone morphogenic protein

controls programmed cell death - removal of protein causes webbing of fingers and toes

Question 15

Growth of bones

Answer 15

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

Question 16

Development of vasculature

Answer 16

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

Question 17

Development of nerves

Answer 17

spinal nerves migrate/grow into limb - eventually innervate dermatomes

Question 18

Development of musculature

Answer 18

muscle precursors migrate from somite (initially no muscle precursors in limb)

Lbx1 gene required for correct migration (when removed, no muscle mass developed)

Question 19

somite

Answer 19

bilateral blocks of mesoderm which run from head to tail of embryo

Question 20

AER stands for

Answer 20

apical ectodermal ridge

Question 21

ZPA stands for

Answer 21

zone of polarising activity

Question 22

Effect of thalidomide

Answer 22

(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

Question 23

DDH - developmental dysplasia of hip

Answer 23

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

Question 24

Growth of long bones

Answer 24

1. initially comprised of hyaline cartilage
2. primary centre of ossification starts (centrally)
3. secondary centre of ossification (at ends of long bone)