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developmental biology > limb development > Flashcards

limb development Flashcards

1
Q

what is the proximal-distal axis of the limb

A 
proximal = shoulder
distal = tips of fingers
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2
Q

what is the anterior-posterior axis of the limb

A 
anterior = thumb
posterior = pinky
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3
Q

what is the dorsal-ventral axis of the limb

A 
dorsal = back of hand 
ventral = palm
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4
Q

where is the limb field derived from?

A

lateral mesoderm

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5
Q

what experiments would you conduct to show that the determination of the limb field is an intrinsic property of the lateral mesoderm?

A

graft mesoderm from prospective limb into ectopic position —> limb formed
graft tissue not normally forming limb into a position fated to form limb —> limb not formed

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6
Q

which t-box TF is expressed in the forelimb

A

tbx5

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7
Q

what does the hindlimb give rise to?

A

leg bud

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8
Q

which t-box TF is expressed in the hindlimb

A

tbx4

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9
Q

what does the forelimb give rise to?

A

wing bud

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10
Q

which gene drives hindlimb identity

A

pitx1

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11
Q

which gene marks where the forelimb will form?

A

hoxc6

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12
Q

describe how limb formation is initiated

A
  1. hox proteins along AP axis determines position of future limb field —> hindlimb or forelimb?
  2. hox drives tbx expression via RA
  3. tbx TFs drive fgf10 expression in lateral mesoderm
  4. fgf10 drives fgf8 expression in ectoderm
  5. fgf8 secreted by AER drives fgf10 expression in lateral mesoderm and promotes cell proliferation of lateral mesoderm cells
  6. wnt signalling restricts size of fgf10 expression domain
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13
Q

what is the progress zone?

A

area of mesenchymal cells lying immediately behind the AER

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14
Q

what is the AER and what is it required for?

A

thickening of ectoderm overlying limb field
fgf rich region
needed for limb outgrowth
high FGF expression levels

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15
Q

what is the progress zone model?

A

AER drives cell proliferation of progress zone behind it

more cell divisions = more distal structures formed

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16
Q

why is the progress zone model incorrect?

A

in the early developing limb field there are already progenitors that can develop all skeletal elements

17
Q

what is the two signal model?

A
  1. initially have all progenitors for all skeletal elements of limb
  2. the cells adopt cell fate based on their position along antagonising FGF and RA signalling gradients –> determines whether the cells will form proximal or distal structures
18
Q

describe the antagonising signalling gradients involved in PD patterning of limb

A

AER = high FGF = most distal
lateral plate mesoderm + paraxial mesoderm = high RA = most proximal
cell fate depends on their position along the gradients

19
Q

what genes does RA signalling activate during PD patterning of limb?

A

meis1

meis2

20
Q

what genes does FGF signalling activate during PD patterning of limb?

A 
hox13 = distal
hox11 = proximal
21
Q

what is the drosophila ortholog of hoxd13?

A

distalless

22
Q

what is the drosophila ortholog of meis?

A

homothorax

23
Q

what would be observed if the zpa or shh soaked bead is transplanted into the anterior limb?

A

mirror image duplication

24
Q

what would be observed in limbs with Shh KO?

A
  • loss of distal skeletal elements + severe truncation
  • anterior most digit only observed
  • loss of identity of zeugopod –> single bone formed
25
Q

which gene is expressed in the dorsal limb?

A

wnt7a

26
Q

which gene is expressed in the ventral limb and what drives its expression?

A

engrailed1 is expressed in the ventral limb

bmp signalling drives engrailed expression

27
Q

where is lmx1b expressed in the limb?

A

dorsal half of the limb

28
Q

what is the role of engrailed1 in patterning the limb?

A

inhibits wnt7a expression

restricts wnt7a expression to dorsal ectoderm

29
Q

what does lateral mesoderm contribute to?

A

limb skeleton formation

developmental biology (12 decks)

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