Upper Limb Development

Question 1

what is a limb?

Answer 1

appendage of the body

Question 2

what is the delay between development of upper and lower limb?

Answer 2

1-2 days

Question 3

HOX genes control what?

Answer 3

the fundamental processes of development and have been conserved throughout the whole animal kingdom. They ensure that the right limbs grow out of the right place.

Question 4

what control limb development?

Answer 4

HOX genes, gene activation and transcription, and signalling via proteins and growth factors

Question 5

what is the term for when fingers are fused together?

Answer 5

syndactyl

Question 6

what is nail patella syndrome?

Answer 6

when there are no nails and no patella - this is due to an abnormality of patterning processes that determine back from front of body - there are abnormalities in the structures of extensor surfaces

Question 7

when do the limbs start to develop?

Answer 7

at 4 weeks a bud will come out of the wall

Question 8

what has happened by 6 weeks?

Answer 8

the limb starts to resemble a normal limb and will have a proximal and some distal hand parts

Question 9

what has happened by 8 weeks and what has not?

Answer 9

by 8 weeks to the eye the limb is formed, however the bones are not yet ossified and muscles not fully developed

Question 10

what does mesoderm give rise to?

Answer 10

skeletal muscles in limb

Question 11

what are the separations of mesoderm?

Answer 11

condensations and somites and notochord

Question 12

where do the limb muscles arise from?

Answer 12

somites

Question 13

what does lateral plate mesoderm give rise to?

Answer 13

bone and cartilage

Question 14

what do somites split into?

Answer 14

sclerotome, myotome and dermatome

Question 15

which nerves supply the back muscles?

Answer 15

dorsal rami of spinal nerves

Question 16

what is classified as outpouchings from the venterolateral body?

Answer 16

limb buds at 4 weeks

Question 17

what is the bud initially comprised of?

Answer 17

core of tissue from lateral plate mesoderm covered by a layer of ectoderm

Question 18

what are the condensations of the mesoderm?

Answer 18

posterior - extensors and anterior - flexors

Question 19

what are the nerves for a) the UL buds and b) the LL buds?

Answer 19

ventral primary rami of spinal nerves C5-T1 and ventral primary rami of L1-S3

Question 20

which limb has more extreme rotation?

Answer 20

LL

Question 21

what is a dermatome?

Answer 21

an area of skin supplied by a single spinal nerve

Question 22

what direction does the limb elongate in?

Answer 22

proximal distal

Question 23

where does the FGF 10 come from?

Answer 23

fibroblast growth factor 10 comes from the mesenchymal core of the limb bud during proximodistal outgrowth and induces a thickening of the overlying ectoderm along tip of limb bud making the apical ectodermal ridge

Question 24

what does the AER express and what does this cause?

Answer 24

FGF 4 and 8 - cause the rapid proliferation of mesenchymal cells underlying the AER - progress zone

Question 25

what does the progress zone maintain?

Answer 25

proximodistal outgrowth of the limb

Question 26

define meromelia?

Answer 26

the partial absence of a limb due to the later or partial loss of FGF signalling/ AER disruption

Question 27

what is the complete absence of a limb and why does it occur?

Answer 27

amelia - very early failure of FGF signalling/ AER disruption. Therefore the progress zone does not develop and there is no proximodistal outgrowth

Question 28

what does failure of the middle of the AER to form properly cause?

Answer 28

cleft hand/foot

Question 29

what is the clinical presentation of cleft hand/foot?

Answer 29

3rd digit is usually completely absent and sometimes there is fusion of the 1st/2nd and 4th/5th digits

Question 30

what does ectopic FGF induce?

Answer 30

supernumerary limbs

Question 31

what does misexpression of HOX lead to?

Answer 31

limbs can develop in wrong places meaning the muscle is not developed and function is impaired

Question 32

what is craniocaudal patterning determined by?

Answer 32

small region of mesenchyme in the caudal part of the limb bud - the zone of polarising activity - where sonic hedgehog is expressed

Question 33

in what direction does SHH diffuse from ZPA?

Answer 33

cranial direction

Question 34

what structures do the concentrations of SHH induce?

Answer 34

low = cranial and high = caudal

Question 35

what does ectopic ZPA/SHH result in?

Answer 35

polydactyl

Question 36

what expresses Wnt7 and in what process?

Answer 36

expression of Wnt7 is from dorsal ectoderm during dorsoventral patterning

Question 37

which gene is activated by Wnt7?

Answer 37

LMX1 which specifies the development of cells becoming dorsal structures

Question 38

what does ventral ectoderm express?

Answer 38

Engrailed-1

Question 39

in which week are digits starting to present?

Answer 39

week 6

Question 40

what is the process that prevents webbing of feet/hands?

Answer 40

apoptosis

Question 41

what is syndactyl?

Answer 41

fused digits due to failure of normal apoptosis

Question 42

what is the frequency of abnormalities in limb development?

Answer 42

6 in every 10000 live births

Question 43

list some causes of abnormalities?

Answer 43

teratogens, drugs, amniotic band syndrome, maternal illness, environmental poisons, unknown, achondroplasia, genetics

Question 44

what does thalidomide cause and what are the presenting symptoms?

Answer 44

phocomelia - proximal elements of limb are absent