Limb development Flashcards

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1
Q

What are the 3 axes of limbs?

A

Proximal-distal
Anterior-posterior (thumb-pinkie)
Dorsal-ventral (palm-knuckle)

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2
Q

What are the 3 types of bones in a tetrapod limb?

A

Stylopod (1 bone), zeugopod (2 bones), autopods (many bones)

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3
Q

Is the limb anatomy of tetrapods a homologous or analogous feature?

A

Homologous, it existed in Tiktaalik

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4
Q

What genes specify limb regions?

A

Hox genes

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5
Q

What happens if a Hox gene that specifies parts of the limb are mutated?

A

Only affects that one region of the limb

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6
Q

Much of the limbs come out of which type of mesoderm?

A

Lateral plate

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7
Q

What are the 3 steps to form a limb bud?

A
  1. Trunk mesoderm is specified to form a limb
  2. Tbx transcription factors act as intermediate signals
  3. Limb bud initiation
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8
Q

What signals specify the trunk mesoderm to form a limb bud?

A

Retinoic acid, FGF, and a posterior to anterior Hox gene code

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9
Q

What do both Tbx transcription factors do?

A

Cause an EMT in future limb cells

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10
Q

Which transcription factor specifies the forelimb?

A

Tbx5

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11
Q

Which transcription factor specifies the hindlimb?

A

Tbx4

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12
Q

How does limb bud initiation happen?

A

Fgf10 is released from the lateral plate mesoderm, which signals the ectoderm to produce Wnt3a. Wnt3a causes the ectoderm to produce Fgf8. Fgf8 causes the mesoderm to produce more Fgf10

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13
Q

Which signal is released from the lateral plate mesoderm to cause initiation of the limb bud?

A

Fgf10

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14
Q

What does Fgf10 do?

A

Signals the mesoderm to produce Wnt3a

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15
Q

What does Wnt3a do?

A

Signals the ectoderm to produce Fgf8

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16
Q

What does Fgf8 do?

A

Signals the mesoderm to produce more Fgf10

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17
Q

What happens if we put an FGF bead between the forelimb bud and the hindlimb bud?

A

Forms a new chimeric limb with both forelimb and hindlimb traits

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18
Q

What does the apical ectodermal ridge do?

A

Maintains proximal-distal growth and expansion in the limb

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19
Q

What types of molecules are expressed in the apical ectodermal ridge?

A

Molecules that define the anterior-posterior axis in the limb

20
Q

What happens if you remove the apical ectodermal ridge?

A

Limb growth stops

21
Q

What happens if you add another apical ectodermal ridge?

A

The limb gets duplicated along the anterior-posterior axis

22
Q

What happens if you transplant the apical ectodermal ridge from the hindlimb to the forelimb and replace the AER of the forelimb?

A

The forelimb develops as a hindlimb instead

23
Q

What happens if you transplant generic mesenchyme tissue into the limb and replace the AER?

A

Limb growth stops

24
Q

What determines the limb structure that mesenchyme cells will become?

A

Their location

25
Q

What are the 3 domains along the proximal-distal axis of a developing limb?

A

Frozen domain, active domain, inhibitory domain

26
Q

What happens if you replace the apical ectodermal ridge with a bead that’s releasing FGF?

A

Limb growth occurs as normal

27
Q

What happens in the frozen domain of a limb?

A

The tissue is already determined and specified to become bone or muscle

28
Q

What happens in the active domain of a limb?

A

The FGF signal is moving away, and TGF-beta is allowed to be expressed, causing cell specification

29
Q

What happens in the inhibitory domain of a limb?

A

The AER and underlying mesoderm is driving growth and is producing FGF and stopping cell specification

30
Q

How do cells get from the inhibitory domain to the active domain?

A

When the cells in the inhibitory domain are dividing, they push the AER away and cells can become specified once they’re out of range of the FGF being produced by the AER

31
Q

Why is Turing’s Reaction Diffusion Model able to predict why the autopod bones branch like they do?

A

Because TGF-beta produces its own inhibitors and also promotes its own activity, leading to predictable patterns

32
Q

What determines if a limb is long or short?

A

How long the AER is active and the concentration of signals

33
Q

What does the zone of polarizing activity do?

A

Specifies the posterior limb bud mesoderm and creates the anterior-posterior axis

34
Q

What happens if you transplant a second zone of polarizing activity onto a limb?

A

Creates a second anterior-posterior axis

35
Q

What signal does the zone of polarizing activity produce?

A

Shh

36
Q

How does digit specification happen?

A

Shh gradient from posterior to anterior

37
Q

How do different digits get specified?

A

How much Shh is around and how long the cells are exposed

38
Q

What digit gets specified when there is no Shh signalling?

A

Anterior phenotype - thumb

39
Q

Where is BMP being produced? Why is it there?

A

Produced by mesoderm between the digits. Shh signalling allows it to be expressed

40
Q

How does BMP signalling help establish digit identity?

A

Allows the right type of cartilage to be expressed in the correct place

41
Q

What signal specifies dorsal tissue in a limb? What produces it? What does it signal to?

A

Wnt7a. Produced in the ectoderm and stays in the ectoderm

42
Q

What transcription factor produces a dorsal phenotype?

A

Lmx1b

43
Q

What is Nail-Patella syndrome?

A

Interruption of Wnt signalling that reduces the dorsal phenotype of the limb

44
Q

What effect do growth hormones have on a limb?

A

Causes expansion of cartilage tissue in the bone growth plate and lengthens the limb

45
Q

What effect does estrogen have on a limb?

A

Low levels stimulate bone growth, but high levels cause chondrocyte death and the bone growth plate to close