Limb Development

Question 1

Overview of Limb Development

Answer 1

• Limbs grow within the AP body axis
• All vertabrates possess four limbs

Question 2

Limb Growth follows Proximal to Distal Axes

Answer 2

• stylopod: Most Proximal
• Zeugopod: Intermediate sections
• Autopod: Most Distal

Question 3

Limb Fields and Bud Formation

Answer 3

• limbs grow from limb fields
• Cells Migrate into the limb bud, forming muscle, bones, and pigmentation from:

Hypaxial myotome: Muscle
Lateral plate Mesoderm: Bones
Neural Crest Cells: Pigmentation

Question 4

limb bud formation

Answer 4

form via interaction b/w mesenchyme and ectoderm

Question 5

Fgf10 function in limb bud formation

Answer 5

initiates limb bud formation in limb mesenchyme, with feedback form the ectoderm

Question 6

Hox Genes and Limb Growth

Answer 6

• determine limb positionaing along AP axis
• low Hox = anterior regions
• High Hox = posterior regions

Hox genes also control forelimb (hox5/6) and hindlimb (Hox9/10) development

Question 7

Retinoic Acid (RA) gradients in limb growth

Answer 7

High RA at posterior; Low at Anterior

Hox genes are activated as limbs grow distally away from the RA gradients

Question 8

Key Molecular Signals

Answer 8

Tbx5: Forelimb specifications
Tbx4: hindlimb Specification

interaction of Fgf10 and Tbx5/4 determines limb identity

Question 9

Apical Ectodermal Ridge (AER)

Answer 9

Critical for distal limb growth
- signals (Fgf8) from AER maintain proliferation in the Progression Zone (PZ)

• Removal of AER halts distal Development, But Fgf8 can substitute spatially

Question 10

Zone of Polarizing Activating (ZPA)

Answer 10

polarizes limb (AP) orientation using Shh gradients

• BMP gradients contribute to digit and AP patterning

Question 11

Proximal - Distal Patterning Information

Answer 11

Mediated by PZ and Hox genes
- older PZ cells retain positional memory via HOX genes

• PZ transplant experiments highlights its role in positional identity

Question 12

Anterior-Posterior Limb Patterning

Answer 12

Requires ZPA and Shh
- BMP gradients contribute to interdigital identity

Question 13

Dorsal-Ventral Patterning

Answer 13

Wnt7a: present on dorsal side, activates Lmx1b for dorsal identity.

• ventral- only limbs impair proper function

Question 14

Apoptosis

Answer 14

• sculpts limbs
• removing webbing between digits
• triggered by BMP2, BMP4, BMP7 in interdigital zones
• Noggin suppresses BMP-induced Apoptosis in digits, ensuring proper shaping

Question 15

AER Removal

Answer 15

stops distal development unless replaced by fgf8

Question 16

ZPA manipulation

Answer 16

Duplication of posterior limb structures

Question 17

PZ transplantation

Answer 17

Alters limb type (hindlimb PZ transplanted to forelimb creates hindlimb)

Question 18

RA and HOX expression

Answer 18

RA-treated severed frog tails can grow limbs, demonstrating hox role in positional cues