Limb development Flashcards
what gives rise to the humerus?
stylopod
what gives rise to the radius and ulna?
zeugopod
what gives rise to the wrist bones, palm bones and digit bones?
distal autopod
is the back of the hand dorsal or ventral?
dorsal
is the palm of the hand dorsal or ventral?
ventral
what is grieg syndrome?
polydactyly and syndactyly
what causes grieg syndrome?
mutation in GL13
what is apert syndrome?
syndactyly
what causes apert syndrome?
mutations in FGFR2
what is holt-oram syndrome?
phocomelia
what causes holt-oram syndrome?
mutations in TBX5
what did thalidomide cause?
phocomelia
when was thalidomide given to women?
1956-1961
how many babies did thalidomide affect?
around 2000 (only 500 survived)
when do forelimb bids form?
24th day
when do hindlimbs form?
28th day
what are the limb buds formed of?
epidermal jacket enclosing lateral plate mesoderm
what does the mesoderm form in the limbs?
most of tissues (bone, tendons, ligaments, dermis, muscle sheaths and blood vessels)
what is the position of the limb buds determined by?
hox genes
what does AER stand for?
acpical ectodermal ridge
where does the AER form?
at the distal end of the limb bud
what type of cells is the AER made of?
columnar cells
what are TBX5 and TBX4?
transcription factors
where is TBX5 transcribed?
forelimbs
where is TBX4 transcribed?
hindlimbs
what do mutations in TBX5 cause?
Holt-Oram syndrome (only affects forelimbs)
what do mutations in TBX4 cause?
patella syndrome (affects bones of hips and legs)
what forms limb muscle?
hypaxial myotome
when do mytome cells migrate into limb buds?
5th week of development
what does the myotome initially form?
large dorsal and ventral condensations
what does the dorsal muscle mass form?
extensors and supinators of forelimb and extensors and abductors of hindlimbs
what does the ventral muscle mass form?
flexors and pronators of forelimb and flexors and adductors of hindlimb
which spinal nerves innervate the muscles of the forelimbs?
C5-T2
which spinal nerves innervate the muscle of the hindlimbs?
L4-S3
how many motor neurons innervate a single myotome during development?
at least 2
how many motor neurons innervate a single mytome in an adult?
1 (all but one retracted soon after birth)
which bones differentiate first?
humerus and femur
what is the order of differentiation?
humerus/femur, radius + ulna/tibia + fibula, carpals/tarsels, metacarpals/metatarsels and finally, phalanges
which digit differentiates first?
4
what is the order of digit differentiation?
4, 3, 2 then 1 and 5 at same time
what is required for limb outgrowth?
AER
what will the removal of AER create?
a distally truncated limb as it will stop limb bud outgrowth
what is AER the source of?
mitogen
what is the mitogen responsible for promoting?
cell division in limb bud mesenchyme
what is a mitogen?
an extracellular system that instructs cells to undergo mitosis
if AER is removed early, what is formed?
the humerus
if AER is removed late, what is formed?
the humerus, radius and ulna
what is the mitogen involved in limb bud outgrowth?
FGF
what does FGF do in the limb?
it diffuses into the limb bud mesenchyme and stimulates call proliferation, thereby promoting limb outgrowth
FGF is essential for limb outgrowth. true or false?
true
does FGF act as a morphogen?
there is some evidence to suggest this - phalanges receive highest concentration, radius and ulna receive the lowest and the humerus grows irrespective of FGF
John Saunders grafted a posterior mesenchyme into an anterior mesenchyme. what was formed?
a duplicate set of digits, with mirror image symmetry
what is the organising centre for patterning the anterior-posterior axis of the limb bud?
the posterior margin, also known as the ZPA
what does ZPA stand for?
zone of polarising activity
what digit forms in the absence of a morphogen?
the thumb
what is the morphogen in the limb buds?
SHH
where is shh expressed?
in the ZPA
shh mimics ZPA grafts when expressed in anterior mesenchyme. true or false?
true
how does shh specify digits?
in a concentration dependant manner
shh is required for limb development. true or false?
true
what defect can shh cause?
preaxial polydactyly
what is preaxial polydactyly?
an extra digit on the side of the thumb
what type of mutation causes preaxial polydactyly?
gain-of-function mutation which affects the enhancer controlling shh production in the zpa
what is acheiropodia?
absense of distal elements of the limbs
what causes acheiropodia?
deletion of DNA that controls expression of shh in zpa
what removes the flaps of skin that connect the digits of an embryo?
apoptosis
what is apoptosis?
programmed cell death
what is syndactyly?
when two or more digits are fused together
what causes syndactyly?
lack of apoptosis in interdigital region during embryogenesis
between which digits is syndactyly most common?
3rd and 4th
what are limb buds formed by?
the proliferating cells of the outer somatopleuric layer of the lateral plate mesoderm
what attracts hypaxial myoblasts to the limb bud?
hepatocyte growth factor (HGF)
what secrets HGF?
limb bud mesenchyme
