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Lecture 1: Limb development Flashcards

embryology of upper limb development

1
Q

what are HOX genes?

A

primitive set of genes that are involved in determining structural differentiation in the body during development.

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2
Q

what happens when there is an abnormality in the HOX gene?

A

abnormalities in developement

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3
Q

what is polydactyly?

A

extra digits

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4
Q

what is nail patella syndrome?

A

under development of structures n the back of the hand, arms, legs
(affects whole dorsum)
The nails are very small and missing patella are key characteristics.

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5
Q

when do limb out-pouches develop?

A

week 5

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6
Q

what are the limb pouches like in week 6?

A

slender and look like the upper limb

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7
Q

what are the limb pouches like in week 8?

A

fully developed limb (smaller scale)

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8
Q

name the different parts of the mesoderm?

A
  1. paraxial mesoderm/somite
  2. intermediate mesoderm
  3. lateral plate mesoderm
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9
Q

what do the somites develop into?

A

limb muscles

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10
Q

what do the lateral plate mesoderm develop into?

A

limb bones and connective tissues

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11
Q

what are the divisions of a somite called?

A

sclerotome - ventral-anterior (ventral column)

dermomyotome - dorso-lateral

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12
Q

what are the sub-divisions of the dermomyotome?

A

dermatome - dermis of skin

myotome - skeletal muscle

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13
Q

what does the dorsal myotome give rise to?

A

back muscles

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14
Q

what does the anterior myotome give rise to?

A

muscles on ventral wall

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15
Q

what is the nerve supply to the back muscles?

A

dorsi rami of spinal nerves

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16
Q

what is the nerve supply to the thoracic and abdominal wall muscles?

A

ventral rami of spinal nerves

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17
Q

what are limb buds?

A

outpouching from the ventrolateral body wall

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18
Q

what do the limb buds initially contain?

A

core tissue from lateral plate mesoderm.

this lateral plate mesoderm migrates into the limb bud and start to pattern out tendons and bones –> template for the limbs.

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19
Q

what is the loose mesenchyme of the limb bud covered by?

A

ectoderm

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20
Q

what does the mesoderm core differentiate into?

A

bones and connective tissue of the limb

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21
Q

what happens to the mesoderm that migrates to from the limb muscles?

A

divides into 2 parts:
1 . posterior condensation
2. Anterior condensation

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22
Q

what does the posterior condensation differentiate into?

A
  • extensors and supinators of upper limb

- extensors and abductors of lower limb

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23
Q

what does the anterior condensation differentiate into?

A
  • flexors and pronators of upper limb

- flexors and adductors of lower limb

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24
Q

what branch of the spinal cord give branches to innervate the upper limb buds?

A

ventral primary rami of spinal nerves C5-T1 (brachial plexus)

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25
what branch of the spinal cord give branches to innervate the lower limb buds?
ventral primary rami of spinal nerves L1-S3 (lumbosacral plexus)
26
which direction do the lower limbs rotate during development?
inwards
27
which direction do the upper limbs rotate during development?
outwards
28
how many axes do limbs develop along?
3
29
what are the axes for limb development
- Proximodistal – from the shoulder to the hand (and from the hip to the foot) - growth in length - Craniocaudal – head to toe growth. thumb grows on radial (lateral) side and little finger develops medially - Dorsoventral – the palm of the hand and sole of the foot are ventral and the knuckle side of the hand and foot are dorsal
30
what is proximodistal outgrowth?
growth from proximal to distal
31
what is FGF10?
fibroblast growth factor. | factor secreted by the mesenchumal core of the limb buds
32
what is AER?
apical ectodermal ridge. | overlying ectoderm along the tip of the limb bud
33
what is the function of FGF?
induces ridge of cells on the very distal end of developing limb (AER).
34
what factors does the AER express?
FGF 4 + 8
35
what is the function of FGF4 + 8
cause rapid proliferation of mesenchymal cells underlying the AER – the progress zone.
36
what does the proximal zone do?
maintains proximodistal outgrowth of the imb
37
what is FGF10 expressed by?
mesoderm
38
what happens if AER is removed?
development is stopped
39
what conditions occur if AER is removed?
- Meromelia | - Amelia
40
what is Meromelia? cause?
partial absence of a limb. late or partial loss of FGF signalling/ AER disruption = arrest of proximodistal outgrowth. can also be caused by vascular abnormalities
41
what is Amelia? cause?
complete absence of limb. | early failure of FGF signalling/ the AER. The progress zone does not develop and there no proximodistal outgrowth.
42
what is Cleft hand/foot?cause
Split hand/foot. | failure of the middle of the AER to develop properly
43
what happens when central AER is missing?
Clefting of hand or foot
44
what is ectopic FGF?
induces supernumerary limbs
45
what is supernumerary limbs? cause?
``` extra limbs cause: -genetic -environmental -(exact cause unknown) ```
46
what is craniocaudal patterning?
explains why the thumb is lateral and the little finger is medial
47
what determines craniocaudal patterning?
zone of polarising activity
48
what is the zone of polarising activity (ZPA)?
small region of mesenchume in the caudal part of the limb bud responsible for determining craniocaudal patterning
49
where is sonic hedgehog is expressed?
the zone of polarising activity.
50
what is sonic hedgehog?
diffuses from the ZPA in a cranial direction.
51
what does high Conc. of SHH induce?
caudal structures e.g. little finger
52
what does low Conc. of SHH induce?
cranial structures e.g. thumb
53
what happens if there is inappropriate/ectopic SHH expression?
two sets of digits in a mirror pattern (polydactyly) | -mirror image because of diffusion gradient
54
what does the dorsal ectoderm express?
Wnt7
55
what does Wnt7 induce?
activation of the gene LMX1
56
what does LMX1 essential for?
specifies the development of cells that become dorsal structures.
57
what do the ventral ectoderm express?
Engrailed-1
58
what does Englrailed-1 inhibit?
Wnt7 | inhibit the development of dorsal structures on ventral side.
59
Nail patella syndrome what is the defect? Main characteristics?
- Rare syndrome affecting nails, bones, kidneys, and eyes - defect in LMX-1 B gene - absent or small, irregular patellae, abnormal nails.
60
what happens to the digits in week 6?
terminal portion of limb buds flatten to form hand and foot plates
61
how are digits formed?
selective apoptosis -the digits form because of apoptosis in the centre. however, there are still growth of fingers because of AER in split into 5 portions.
62
syndactyly
fused digits due to failure of normal apoptosis
63
which drugs affect normal limb development
Teratogens: - Thalodomide --> was used to cure mornig sickness - sodium valproate ---> antiepileptic - warfarin - cyproterine acetate --> potent steroidal ani-androgen used for severe achne --> Vitamin K (?) - NSAIDS--> premature risk of closure of the dugs arteriosus, risk of miscarriage - radiation, agent orange - environment: smoking/drinking
64
what other factors affect normal limb development?
- genetics--> hereditary or spontaneous mutations - maternal illness - amniotic band syndrome - unknown cause in many cases
65
Achondraplasia
long bones of the limbs are shorter
66
Amniotic band syndrome
bits of the placenta get tangled in the digits/limb = cut off blood supply
67
phocomelia
- digits develops prematurely | - proximal elements of limb absent
68
what are the causes of phocomelia?
- genetic factors | - teratogens --> commenly thalidomide (inhibits the expression of FGF10 and 8 and thoughts to inhibit angiogenesis)
69
what is thalidomide still used for?
leprosy --> chronic, progressive bacterial infections (bacteria: mycobacterium leprae) multiple myeloma --> cancer of plasma cells used with access to strong contraceptives

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