Limb Development

Question 1

What are the three regions of limb development?

Answer 1

The three regions are:
Stylopod
Zeugopod
Autopod

Question 2

Where do limb buds emerge from?

Answer 2

Limb buds emerge from the flank of the embryo

Question 3

What are the key developmental events in limb development?

Answer 3

the key events are:
Initiation
Outgrowth
Patterning
Morphogenesis
Differentiation

Question 4

Define stylopod, zeugopod, and autopod

Answer 4

Stylopod: The proximal region of the limb (e.g., humerus bone in the upper limbs).
Zeugopod: The middle region of the limb.
Autopod: The distal region of the limb.

Question 5

Where do limb buds emerge from?

Answer 5

Limb buds emerge from the flank of the embryo

Question 6

What is the first event in limb development?

Answer 6

The initiation of limb development

Question 7

What is the process of limb growth called?

Answer 7

Outgrowth, where the limb elongates and expands

Question 8

What is patterning in limb development?

Answer 8

Patterning refers to the organization and arrangement of tissues and structures within the limb

Question 9

What is morphogenesis in limb development?

Answer 9

Morphogenesis involves the shaping and formation of the limb’s overall structure.

Question 10

What happens during limb differentiation?

Answer 10

Cells become specialized to form specific tissues and structures in the limb.

Question 11

Where do limb buds originate?

Answer 11

Limb bud cells originate from the flank of the lateral plate mesoderm

Question 12

What does the wing barrier operation in chicks demonstrate?

Answer 12

• The wing barrier operation in chicks involves a foil barrier that prevents limb bud formation in the wing region.
• Result: No limb outgrowth and no wing formation.
• Conclusion: Signals from neighboring tissues (somites + intermediate mesoderm) induce limb bud formation.
  Flashcard 3

Question 13

What happens when FGF-soaked beads are implanted in the flank of a chick embryo?

Answer 13

• The embryo grows an extra limb, indicating FGF induces ectopic limb formation.
  Question: Which FGF gene is responsible for this effect?

Question 14

What is the role of FGF10 in limb development?

Answer 14

Result: No forelimb or hindlimb formation when FGF10 is absent.
Conclusion: FGF10 is required for limb development.

Question 15

What are the three main axes that pattern limb development?

Answer 15

The three main axes are:
Antero-posterior (AP) axis
Dorso-ventral (DV) axis
Proximal-distal (PD) axis

Question 16

What is the role of the Apical Ectodermal Ridge (AER) in limb development?

Answer 16

The AER signals maintain limb outgrowth and promote the formation of the proximal-distal axis.

Question 17

How does the AER influence limb development?

Answer 17

• Experiment: When the AER is cut off at different stages of development:
  Early stage: Only proximal limb formation occurs.
  Mid-stage: The limb grows more.
  Late stage: The limb bud is almost complete, with only digits missing.
• Conclusion: The AER is required for full limb development.

Question 18

What signaling molecule is highly expressed in the AER?

Answer 18

FGF8 is highly expressed in the AER

Question 19

What happens when FGF8 protein is applied to an early chick embryo with the AER removed?

Answer 19

• Experiment: Early chick embryo with the AER removed is implanted with a bead soaked in FGF8 protein.
• Result: FGF8 rescues limb development, leading to normal wing development.

Question 20

What happens in FGF8+4 knockout mice?

Answer 20

• Experiment: FGF8 and FGF4 are knocked out in mice.
• Result: Severe disruptions in limb formation are observed.

Question 21

What is the Zone of Polarising Activity (ZPA) responsible for in limb development?

Answer 21

The ZPA is responsible for anterior-posterior patterning, found at the posterior margin of the limb bud.

Question 22

Describe the outcome of an experiment involving ZPA transplantation

Answer 22

Experiment: ZPA is transplanted from one embryo into the anterior limb margin of another embryo (resulting in two ZPAs).
Outcome: Double the number of digits, duplicated at a mirror image, are formed in the limb.

Question 23

How does the ZPA influence digit formation in the limb bud?

Answer 23

• Cells closest to the morphogen (Shh) secreted by the ZPA form digit 4, followed by digit 3, then digit 2, and so on along the posterior side of the limb.
• The ZPA provides positional identity to the developing digits.

Question 24

What happens when an ectopic Shh bead is added to the limb bud?

Answer 24

Addition of an ectopic Shh bead leads to the formation of duplicated digits

Question 25

What is the consequence of no Shh expression in the limb bud?

Answer 25

No Shh expression results in no digit formation in the limb

Question 26

How do Shh and FGF4 interact in limb development?

Answer 26

• Shh interacts with FGF4 in limb development, with FGF4 being required to maintain Shh activity.
• Positive feedback loop between signals from ZPA (Shh) and AER (FGF4) coordinates growth simultaneously.

Question 27

What role does the dorsal ectoderm play in limb development?

Answer 27

The dorsal ectoderm provides signals that pattern the dorsal-ventral axis of the limb

Question 28

Describe the outcome of an experiment involving the flipping of limb bud dorsal and ventral ectoderm

Answer 28

• In the experiment, when the limb bud dorsal and ventral ectoderm is flipped, the limb forms inverted.
• This indicates that signals from the dorsal ectoderm are essential for proper limb patterning

Question 29

What is the role of Wnt7a in limb development?

Answer 29

• Wnt7a, expressed in the dorsal ectoderm, induces the expression of Lmx-1 in the dorsal mesenchyme of the limb-

Question 30

What happens when Wnt7a is misexpressed throughout the limb?

Answer 30

• Misexpression of Wnt7a throughout the limb leads to ectopic expression of Lmx-1 throughout the ventral mesenchyme of the limb.

Question 31

What are the consequences of Lmx-1 gene deletion in mice?

Answer 31

• in mice, deletion of the Lmx-1 gene results in the dorsal part of the paw developing like the ventral side, leading to a loss of dorsal limb pattern.

Question 32

Which candidate genes are involved in determining limb identity?

Answer 32

Tbx5 is expressed in the forelimb only, Tbx4 in the hindlimb only, and Pitx1 in the hindlimb

Question 33

Describe the outcome of an experiment involving the deletion of the Tbx5 gene in forelimbs

Answer 33

• When the Tbx5 gene is deleted from forelimbs (knockout), the forelimb fails to develop due to disruption in FGF signaling, which is essential for initiating limb outgrowth.