Limb development

Question 1

What are the 3 axes of limbs?

Answer 1

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

Question 2

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

Answer 2

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

Question 3

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

Answer 3

Homologous, it existed in Tiktaalik

Question 4

What genes specify limb regions?

Answer 4

Hox genes

Question 5

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

Answer 5

Only affects that one region of the limb

Question 6

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

Answer 6

Lateral plate

Question 7

What are the 3 steps to form a limb bud?

Answer 7

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

Question 8

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

Answer 8

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

Question 9

What do both Tbx transcription factors do?

Answer 9

Cause an EMT in future limb cells

Question 10

Which transcription factor specifies the forelimb?

Answer 10

Tbx5

Question 11

Which transcription factor specifies the hindlimb?

Answer 11

Tbx4

Question 12

How does limb bud initiation happen?

Answer 12

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

Question 13

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

Answer 13

Fgf10

Question 14

What does Fgf10 do?

Answer 14

Signals the mesoderm to produce Wnt3a

Question 15

What does Wnt3a do?

Answer 15

Signals the ectoderm to produce Fgf8

Question 16

What does Fgf8 do?

Answer 16

Signals the mesoderm to produce more Fgf10

Question 17

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

Answer 17

Forms a new chimeric limb with both forelimb and hindlimb traits

Question 18

What does the apical ectodermal ridge do?

Answer 18

Maintains proximal-distal growth and expansion in the limb

Question 19

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

Answer 19

Molecules that define the anterior-posterior axis in the limb

Question 20

What happens if you remove the apical ectodermal ridge?

Answer 20

Limb growth stops

Question 21

What happens if you add another apical ectodermal ridge?

Answer 21

The limb gets duplicated along the anterior-posterior axis

Question 22

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

Answer 22

The forelimb develops as a hindlimb instead

Question 23

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

Answer 23

Limb growth stops

Question 24

What determines the limb structure that mesenchyme cells will become?

Answer 24

Their location

Question 25

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

Answer 25

Frozen domain, active domain, inhibitory domain

Question 26

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

Answer 26

Limb growth occurs as normal

Question 27

What happens in the frozen domain of a limb?

Answer 27

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

Question 28

What happens in the active domain of a limb?

Answer 28

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

Question 29

What happens in the inhibitory domain of a limb?

Answer 29

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

Question 30

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

Answer 30

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

Question 31

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

Answer 31

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

Question 32

What determines if a limb is long or short?

Answer 32

How long the AER is active and the concentration of signals

Question 33

What does the zone of polarizing activity do?

Answer 33

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

Question 34

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

Answer 34

Creates a second anterior-posterior axis

Question 35

What signal does the zone of polarizing activity produce?

Answer 35

Shh

Question 36

How does digit specification happen?

Answer 36

Shh gradient from posterior to anterior

Question 37

How do different digits get specified?

Answer 37

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

Question 38

What digit gets specified when there is no Shh signalling?

Answer 38

Anterior phenotype - thumb

Question 39

Where is BMP being produced? Why is it there?

Answer 39

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

Question 40

How does BMP signalling help establish digit identity?

Answer 40

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

Question 41

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

Answer 41

Wnt7a. Produced in the ectoderm and stays in the ectoderm

Question 42

What transcription factor produces a dorsal phenotype?

Answer 42

Lmx1b

Question 43

What is Nail-Patella syndrome?

Answer 43

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

Question 44

What effect do growth hormones have on a limb?

Answer 44

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

Question 45

What effect does estrogen have on a limb?

Answer 45

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