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