20 Limb development II

Question 1

What do Hox genes control in limb development?

Answer 1

Limb segmentation

Hox genes are critical in determining the structure and identity of limb segments.

Question 2

Which Hox gene groups are responsible for specific limb regions?

Answer 2

• Hox9 group: Scapula/pelvic region
• Hox10 group: Stylopod (humerus/femur)
• Hox11 group: Zeugopod (radius-ulna/tibia-fibula)
• Hox12-13 group: Autopod (wrist, fingers/ankle, toes)

Each Hox group corresponds to a specific part of limb development.

Question 3

How do Hox genes exhibit spatial and temporal collinearity?

Answer 3

Activation patterns show sequential activation from 3’ to 5’ ends

This means that genes located closer to the 3’ end of the Hox cluster are activated earlier than those at the 5’ end.

Question 4

What was the effect of Hox11 A&D double knockout in experiments?

Answer 4

Loss of zeugopod (radius/ulna) in forelimb

This highlights the critical role of Hox11 genes in limb development.

Question 5

What are the two key mechanisms regulating Hox gene expression in limb development?

Answer 5

• Gradients of morphogens
• Regulatory elements

Morphogen gradients like retinoic acid and FGFs, along with regulatory elements like the Early Limb Control Region (ELCR), play crucial roles.

Question 6

What gradient does Sonic Hedgehog (Shh) create in limb development?

Answer 6

High concentration posteriorly, low anteriorly

This gradient is essential for digit specification.

Question 7

How does BMP function in limb development?

Answer 7

• Promotes cartilage formation with Wnt signaling
• Induces apoptosis with Wnt inhibitor
• Causes programmed cell death in interdigital mesenchyme

BMPs have context-dependent roles in limb development.

Question 8

What happens during the second wave of Hox expression?

Answer 8

Late in limb development, Shh and BMP gradients activate ‘reverse’ Hox expression

This late expression is crucial for digit formation and identity.

Question 9

What is the role of Wnt7a in dorsal-ventral patterning?

Answer 9

Induces Lmx1 transcription factor in underlying mesoderm

Wnt7a is critical for establishing dorsal structures in limb development.

Question 10

What transcription factors determine forelimb vs. hindlimb identity?

Answer 10

• Tbx5: Forelimb
• Tbx4: Hindlimb
• Pitx1: Hindlimb identity

Tbx5 and Tbx4 are induced by FGF8, while Pitx1 specifies hindlimb characteristics.

Question 11

What experimental evidence supports the role of BMPs in digit separation?

Answer 11

Noggin-soaked beads (BMP inhibitor) alter digit pattern

This demonstrates BMP’s role in regulating digit formation and separation.

Question 12

Fill in the blank: BMPs are part of the _______ superfamily.

Answer 12

TGF-β

BMPs function through specific signaling pathways involving serine/threonine kinase receptors.

Question 13

What is the effect of misexpressing Pitx1 in the forelimb?

Answer 13

Transforms it to hindlimb-like structure

This shows the regulatory influence of Pitx1 on limb identity.

Question 14

How does the Global Control Region (GCR) enhancer function in limb development?

Answer 14

Controls late Hox gene expression pattern

This enhancer is important for proper digit formation and identity in limbs.

Question 15

What defines the anterior-posterior patterning in limb development?

Answer 15

ZPA/Shh gradient

The gradient influences digit identity and positioning.

Question 16

What happens in the case of Wnt7a knockout?

Answer 16

Ventralization of dorsal structures

This indicates the importance of Wnt7a in dorsal patterning.