Limb Development Flashcards
What are the three regions of limb development?
The three regions are:
Stylopod
Zeugopod
Autopod
Where do limb buds emerge from?
Limb buds emerge from the flank of the embryo
What are the key developmental events in limb development?
the key events are:
Initiation
Outgrowth
Patterning
Morphogenesis
Differentiation
Define stylopod, zeugopod, and autopod
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.
Where do limb buds emerge from?
Limb buds emerge from the flank of the embryo
What is the first event in limb development?
The initiation of limb development
What is the process of limb growth called?
Outgrowth, where the limb elongates and expands
What is patterning in limb development?
Patterning refers to the organization and arrangement of tissues and structures within the limb
What is morphogenesis in limb development?
Morphogenesis involves the shaping and formation of the limb’s overall structure.
What happens during limb differentiation?
Cells become specialized to form specific tissues and structures in the limb.
Where do limb buds originate?
Limb bud cells originate from the flank of the lateral plate mesoderm
What does the wing barrier operation in chicks demonstrate?
- 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
What happens when FGF-soaked beads are implanted in the flank of a chick embryo?
- The embryo grows an extra limb, indicating FGF induces ectopic limb formation.
Question: Which FGF gene is responsible for this effect?
What is the role of FGF10 in limb development?
Result: No forelimb or hindlimb formation when FGF10 is absent.
Conclusion: FGF10 is required for limb development.
What are the three main axes that pattern limb development?
The three main axes are:
Antero-posterior (AP) axis
Dorso-ventral (DV) axis
Proximal-distal (PD) axis
What is the role of the Apical Ectodermal Ridge (AER) in limb development?
The AER signals maintain limb outgrowth and promote the formation of the proximal-distal axis.
How does the AER influence limb development?
- 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.
What signaling molecule is highly expressed in the AER?
FGF8 is highly expressed in the AER
What happens when FGF8 protein is applied to an early chick embryo with the AER removed?
- 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.
What happens in FGF8+4 knockout mice?
- Experiment: FGF8 and FGF4 are knocked out in mice.
- Result: Severe disruptions in limb formation are observed.
What is the Zone of Polarising Activity (ZPA) responsible for in limb development?
The ZPA is responsible for anterior-posterior patterning, found at the posterior margin of the limb bud.
Describe the outcome of an experiment involving ZPA transplantation
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.
How does the ZPA influence digit formation in the limb bud?
- 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.
What happens when an ectopic Shh bead is added to the limb bud?
Addition of an ectopic Shh bead leads to the formation of duplicated digits
What is the consequence of no Shh expression in the limb bud?
No Shh expression results in no digit formation in the limb
How do Shh and FGF4 interact in limb development?
- 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.
What role does the dorsal ectoderm play in limb development?
The dorsal ectoderm provides signals that pattern the dorsal-ventral axis of the limb
Describe the outcome of an experiment involving the flipping of limb bud dorsal and ventral ectoderm
- 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
What is the role of Wnt7a in limb development?
- Wnt7a, expressed in the dorsal ectoderm, induces the expression of Lmx-1 in the dorsal mesenchyme of the limb-
What happens when Wnt7a is misexpressed throughout the limb?
- Misexpression of Wnt7a throughout the limb leads to ectopic expression of Lmx-1 throughout the ventral mesenchyme of the limb.
What are the consequences of Lmx-1 gene deletion in mice?
- 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.
Which candidate genes are involved in determining limb identity?
Tbx5 is expressed in the forelimb only, Tbx4 in the hindlimb only, and Pitx1 in the hindlimb
Describe the outcome of an experiment involving the deletion of the Tbx5 gene in forelimbs
- 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.
