Limb Development

Question 1

What does prenatal thalidomide exposure cause?

Answer 1

Children w/ limb development issues and microphthalmia.

Question 2

Which mesoderm is responsible for forming the limb muscle? What about the limb skeleton?

Answer 2

Somitic mesoderm = muscle

Lateral plate mesoderm = skeleton

Question 3

What controls the placement of limbs along the body axis?

Answer 3

Hox gene expression patterning according to the gene’s position on the chromosome.

Question 4

The boundary between ___ and ___ expression is implicated in the forelimb position.

Answer 4

Hox5 and Hox6

Question 5

The boundary between ___ and ___ expression is implicated in the hindlimb position.

Answer 5

Hox 9 and Hox10

Question 6

What 2 processes are involved in the “induction” of limb mesoderm? What is essential for these processes?

Answer 6

1. Delamination (of cells from lateral plate)
2. Migration (to form limb bud)
   Require the presence of fibroblast growth factor (FGF).

Question 7

If you ectopically express FGF in a chick embryo, what occurs?

Answer 7

You get ectopic limb formation at the site of FGF expression.

Question 8

How do Tbx4 and Tbx5 appear to influence the function of FGF in limb development?

Answer 8

Tbx5: specifies forelimb
Tbx4: specifies hindlimb

Question 9

What seems to be the default mature structure for a developing limb?

Answer 9

Forelimb-like morphology.

Question 10

What is Holt Oram syndrome? How is it caused?

Answer 10

Defects in forelimb structure formation caused by Tbx5 mutations.

Question 11

What structure is visible on the limb bud? Is it necessary for limb formation?

Answer 11

The anterior ectoderm ridge (AER). Yes, removal halts limb development.

Question 12

What acts to cause specification of limb identities? Why is the AER required for this?

Answer 12

The underlying mesenchyme specifies identity. The AER expresses Fgf8 which keeps the mesenchyme proliferating.

Question 13

How does expression of Fgf8 affect the limb bud mesenchyme?

Answer 13

Fgf8 keeps the mesenchyme in a proliferative state, otherwise it would stop growing and begin differentiating.

Question 14

What happens if you replace early limb bud mesenchyme with late limb bud mesenchyme in a developing limb bud?

Answer 14

You only get the last part of the limb, all the earlier structures are gone.

Question 15

How are proximal-distal limb fates specified according to the progress zone model?

Answer 15

An intrinsic clock at the leading edge which acts on the mesenchyme along with AER FGFs to change specification at different times.

Question 16

How are proximal-distal limb fates specified according to the two signal model?

Answer 16

Two gradients. Retinoic acid from the proximal domain and FGF from the distal domain each specify. Middle domain under no influence, specifies itself.

Question 17

How are positional cues in the developing limb mediated? Is there redundancy?

Answer 17

By Hox genes. These exhibit redundancy, requiring double knockout for loss of function.

Question 18

In limb development, what does ZPA mean? What is this?

Answer 18

Zone of polarizing activity. Mesenchyme in the posterior limb bud which can specify posterior fates.

Question 19

What is responsible for causing posterior development in the limb?

Answer 19

Shh expression (in the ZPA).

Question 20

How is anterior limb specification accomplished? What goes wrong in a mouse with hemimelic extra toes (Hx)?

Answer 20

Anterior limb bud specified by low Shh from the Shh morphagen gradient.

Question 21

How is AP axis asymmetry/digit identity specified during limb development?

Answer 21

By the duration and concentration of Shh signalling. Shh acts as a morphogen, high in posterior.

Question 22

Why have snakes lost their limbs?

Answer 22

Because they have expanded expression of HoxC8 and HoxC6 to inhibit Hox5B (limb development) along their entire body.

Question 23

What is the function if HoxC8 and HoxC6?

Answer 23

To inhibit Hox5B (limb development) expression in the space between the forelimb and the hindlimb.

Question 24

Do snakes express Shh in their ZPA? Have they lost this ability?

Answer 24

No expression of Shh but they still have the ability.

Question 25

Interaction between the ___ and the ___ stabilizes limb bud progression.

Answer 25

AER and the ZPA.

Question 26

What factors establish the Shh morphogen gradient in posterior limb development? What else maintains Shh levels?

Answer 26

Transcription factor dHAND as well as Fgf8. Wnt7a maintains Shh levels.

Question 27

What effect does BMP have on Fgf8? How does gremlin (Gre) activity effect Fgf8?

Answer 27

Gremlin inhibits BMP, effectively upregulating Fgf8.

Question 28

Through what pathway do researchers suspect thalidomide acts on limb development?

Answer 28

The cereblon pathway.