Upper Limb Development Flashcards
what is a limb?
appendage of the body
what is the delay between development of upper and lower limb?
1-2 days
HOX genes control what?
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.
what control limb development?
HOX genes, gene activation and transcription, and signalling via proteins and growth factors
what is the term for when fingers are fused together?
syndactyl
what is nail patella syndrome?
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
when do the limbs start to develop?
at 4 weeks a bud will come out of the wall
what has happened by 6 weeks?
the limb starts to resemble a normal limb and will have a proximal and some distal hand parts
what has happened by 8 weeks and what has not?
by 8 weeks to the eye the limb is formed, however the bones are not yet ossified and muscles not fully developed
what does mesoderm give rise to?
skeletal muscles in limb
what are the separations of mesoderm?
condensations and somites and notochord
where do the limb muscles arise from?
somites
what does lateral plate mesoderm give rise to?
bone and cartilage
what do somites split into?
sclerotome, myotome and dermatome
which nerves supply the back muscles?
dorsal rami of spinal nerves
what is classified as outpouchings from the venterolateral body?
limb buds at 4 weeks
what is the bud initially comprised of?
core of tissue from lateral plate mesoderm covered by a layer of ectoderm
what are the condensations of the mesoderm?
posterior - extensors and anterior - flexors
what are the nerves for a) the UL buds and b) the LL buds?
ventral primary rami of spinal nerves C5-T1 and ventral primary rami of L1-S3
which limb has more extreme rotation?
LL
what is a dermatome?
an area of skin supplied by a single spinal nerve
what direction does the limb elongate in?
proximal distal
where does the FGF 10 come from?
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
what does the AER express and what does this cause?
FGF 4 and 8 - cause the rapid proliferation of mesenchymal cells underlying the AER - progress zone
what does the progress zone maintain?
proximodistal outgrowth of the limb
define meromelia?
the partial absence of a limb due to the later or partial loss of FGF signalling/ AER disruption
what is the complete absence of a limb and why does it occur?
amelia - very early failure of FGF signalling/ AER disruption. Therefore the progress zone does not develop and there is no proximodistal outgrowth
what does failure of the middle of the AER to form properly cause?
cleft hand/foot
what is the clinical presentation of cleft hand/foot?
3rd digit is usually completely absent and sometimes there is fusion of the 1st/2nd and 4th/5th digits
what does ectopic FGF induce?
supernumerary limbs
what does misexpression of HOX lead to?
limbs can develop in wrong places meaning the muscle is not developed and function is impaired
what is craniocaudal patterning determined by?
small region of mesenchyme in the caudal part of the limb bud - the zone of polarising activity - where sonic hedgehog is expressed
in what direction does SHH diffuse from ZPA?
cranial direction
what structures do the concentrations of SHH induce?
low = cranial and high = caudal
what does ectopic ZPA/SHH result in?
polydactyl
what expresses Wnt7 and in what process?
expression of Wnt7 is from dorsal ectoderm during dorsoventral patterning
which gene is activated by Wnt7?
LMX1 which specifies the development of cells becoming dorsal structures
what does ventral ectoderm express?
Engrailed-1
in which week are digits starting to present?
week 6
what is the process that prevents webbing of feet/hands?
apoptosis
what is syndactyl?
fused digits due to failure of normal apoptosis
what is the frequency of abnormalities in limb development?
6 in every 10000 live births
list some causes of abnormalities?
teratogens, drugs, amniotic band syndrome, maternal illness, environmental poisons, unknown, achondroplasia, genetics
what does thalidomide cause and what are the presenting symptoms?
phocomelia - proximal elements of limb are absent
