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Tetrapod Limb Development. Revisiting Axis specification Limb Formation and Growth Digit Formation. The tetrapod limb. stylopod. zeugopod. autopod. Limb Development in 4 dimensions. Proximal-Distal axis Anterior Posterior axis Dorsal-Lateral axis Time. Limb bud Specification. - PowerPoint PPT Presentation
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Tetrapod Limb Development• Revisiting Axis specification• Limb Formation and Growth• Digit Formation
The tetrapod limb
stylopod
zeugopod
autopod
Limb Development in 4 dimensions• Proximal-Distal axis• Anterior Posterior axis• Dorsal-Lateral axis• Time
Limb bud Specification• Limb bud fate mapping
– Removal– Transplantation– Cell/Tissue tracking
• Limb Field• Limb Bud formation• Hox genes: Hox 6 and
Forelimb
Limb Bud: Lateral plate mesoderm
Multilimbs arise from dividing the bud
Induction of limb bud formation• Fgf8• Wnt2b/8c and Fgf10
Induction of Limb Bud
Forelimb or Hindlimb?• Tbx transcription factors: Tbx5 and Tbx4
Genetic Regulation of early limb formation
Hox6
Tbx5
Fgf10
For Forelimb
Proximal-Distal Axis: Anterior ectodermal ridge
AER and Limb bud development• AER major signaling center
for forming Limb.– Ensures plasticity of
mesenchyme– Maintains factors that
determine A-P axis– Contacts A-P/D-V axis
specifiers in order to inform cells how to differentiate
• AER at distal margin of forming limb bud.
• Makes direct contact with mesenchyme underneath (Progress zone-PZ).
AER and Limb development
Role of PZ in Limb growth/specification
Limb Growth
Reaction-diffusion model for proximal-distal limb specification
A-P axis: Sonic Hedgehog• Zone of polarizing activity (ZPA)• Shh expressed in ZPA
A-P axis: Sonic Hedgehog• Zone of polarizing activity (ZPA)• Shh expressed in ZPA
Polydactyly: Shh overexpression?
Digit formation
D-V axis: third and final axis• Wnt7a• Lim1-dorsal specification
regulator
Coordination of the 3 axes
Sculpting the hand• BMPs initiate cell death in interdigital, interior, and anterior-
posterior necrotic zones.
Joint Formation
Fgfs and dwarfism