Making a Limb Flashcards

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1
Q

Limbs are _________ to the body plan

A

Appendages

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2
Q

Which organism is a good model for studying limb development?

A

Chick

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3
Q

What are limb buds?

A

The site for limb growth

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4
Q

Limb buds have what kind of information?

A

Positional and axes info

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5
Q

What processes occur at the limb bud?

A

Cell differentiation, growth, morphogenesis

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6
Q

What are Hox genes?

A

A group of related genes that control the body plan of an embryo

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7
Q

Which gene can be knocked out of mouse making forelimbs develop at a more anterior level?

A

Hoxb5

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8
Q

What does the Hoxb5 gene do and to what organism?

A

If knocked out of mice it causes the forelimbs to develop at a more anterior level

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9
Q

How does knocking out a Hoxb5 gene cause the forelimbs to develop at a more anterior level?

A

Restricts expression of fibroblast growth factors (FGFs) to limb-forming regionss

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10
Q

In chicks is FGF required for limb bud formation?

A

Yes

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11
Q

FGF signalling is ________ for limb bud formation

A

Required/Sufficient

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12
Q

In chicks is FGF sufficient for limb bud formation?

A

Yes

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13
Q

What does the homozygous knockout of FGF10 result in?

A

Embryos lacking limb buds

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14
Q

Which gene can be homozygously knocked out to cause a lack of limb buds in chicks?

A

FGF10

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15
Q

Local application of FGF4 induces what?

A

Ectopic (abnormally located) limb buds

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16
Q

Which gene can induce ectopic limb buds in chicks?

A

FGF4

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17
Q

Limb bud structure

A

Apical Ectodermal Ridge (AER)
Progress Zone (PZ
Zone of Polarising Activity (ZPA)

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18
Q

What is the AER?

A

Apical ectodermal ridge

- Ridge of thickened epithelium around the tip of the limb bud

19
Q

The AER rigid, why?

A

Keeps the limb bud flattened

20
Q

What does the AER maintain?

A

Cell proliferation in the PZ

21
Q

What does removal of the AER result in?

A

Truncation of the limb

22
Q

Does the time of removal of the AER affect the truncation of the limb?

A

If removed at 3 days, only proximal elements of the arm formed. At days, more distal elements formed

23
Q

Can you induce normal development after removing the AER?

A

Yes, replaced the AER with beads soaked in FGF4

24
Q

What happens if you remove the AER and replace with beads soaked in FGF4?

A

Normal development of the limb

25
Q

What is the PZ?

A

Progress Zone

- Distal region of limb bud mesenchyme (mesodermal cells)

26
Q

Is the PZ the distal or proximal region of the limb bud mesenchyme?

A

Distal

27
Q

What are the cells like in the PZ doing?

A

Undifferentiated and rapidly dividing

28
Q

What does the length of time in the PZ determine?

A

Cell fate

29
Q

How is cell fate in the limb bud determined?

A

Length of time in the PZ

30
Q

Along which axis does the length of time in the progress zone determine cell fate?

A

Proximal-distal axis

31
Q

What is the ZPA?

A

Zone of Polarising Activity

- Region of limb bud mesenchyme which is an organising centre to pattern the anterior-posterior axis

32
Q

Which axis does the ZPA pattern?

A

Anterior-posterior axis

33
Q

Where can the ZPA be transplanted to induce symmetrical duplications of normal limb elects about the anterior-posterior axis?

A

Underneath the anterior AER

34
Q

What happens when the ZPA is transplanted underneath the anterior AER?

A

The ZPA induces symmetrical duplications of normal limb elements about the anterior-posterior axis

35
Q

Which gene is expressed in a very discrete zone of the limb bud?

A

Sonic Hedgehog (SHH)

36
Q

What acts a morphogen in the limb bud?

A

SHH

37
Q

What does SHH pattern by acting as a morphogen?

A

The anterior-posterior axis

38
Q

What can alternatively be done instead of transplanting the ZPA underneath the anterior AER to induce symmetrical duplications of limb elements about the anterior-posterior axis?

A

Implant an SHH-soaked bead as it mimics the action of ZPA

39
Q

Which class of genes are also expressed in overlapping zones of the limb bud?

A

Hox genes

40
Q

What roles do Hox genes have in the limb bud?

A
  • May specify the ZPA
  • Deletion of Hox genes –> loss of SHH expression in ZPA (lead to limb truncation)
  • Transplantation of ZPA establishes new domains of the gene expression in the limb bum
41
Q

What does the deletion of Hox genes lead to?

A

Loss of SHH expression in the ZPA

42
Q

What do transplant experiments demonstrate about the limb bud?

A

That the mesoderm of the limb bud determines the pattern of cell death

43
Q

What regulates the pattern of cell death in limb buds?

A

Hox genes