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#limb outgrowth

3 public questions tagged with this topic.

Limb Development -l

Which experiment demonstrated that Shh signaling is necessary for limb outgrowth?

Necessity of sonic hedgehog signaling for limb outgrowth and anteroposterior patterning was demonstrated through pharmacologic and genetic inhibition approaches. Treatment with cyclopamine blocking Smoothened signal transduction or Shh-null mouse embryos exhibited severely truncated limbs lacking posterior digits 3-5 and premature downregulation of Gremlin1 resulting in increased BMP activity that represses apical ridge FGF expression. Blocking retinoic acid synthesis shifts axial boundaries, ridge removal tests maintenance, Tbx5 overexpression alters identity, but specific SHH inhibition uniquely reveals dual requirement for growth and patterning in tetrapod limbs.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: SHH inhibition – cyclopamine and Shh mutants affecting outgrowth.

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Limb Development -lll

Which molecule is primarily responsible for maintaining AER function and limb outgrowth?

Limb outgrowth is sustained by reciprocal epithelial-mesenchymal feedback between mesoderm and ectoderm. Lateral plate mesoderm expressing Tbx5 Tbx4 under Wnt2b signals expresses FGF10, which signals via FGFR2b to overlying ectoderm, activating Wnt3a and beta-catenin to induce and maintain AER FGF8 expression. FGF10 itself is the crucial mesenchymal inducer that keeps AER functional; its loss causes FGF8 fading, progress zone arrest and severe truncation. Wnt3a induces AER initially, Gremlin antagonizes BMP to prolong AER, BMP4 terminates AER, but maintenance origin lies in continuous FGF10 signaling.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: FGF10 as inducer and maintainer of AER.

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Tetrapod

Which of the following molecules is essential for limb outgrowth in tetrapods?

Limb bud initiation and sustained outgrowth depend on mesenchymal FGF10 induced by TBX5 in forelimb and TBX4-Pitx1-Islet1 in hindlimb. FGF10 activates Wnt3a and beta-catenin in overlying ectoderm, inducing AER formation expressing FGF8. Reciprocal FGF10-FGF8 loop then drives proliferation of progress zone and maintains distal identity. Fgf10 null mice exhibit complete limbless phenotype with no AER induction. Replacement of FGF10 with implanted FGF bead rescues outgrowth, proving necessity and sufficiency. Hence FGF10 constitutes essential initiating and maintenance signal for tetrapod limb outgrowth, elongation and patterning competence.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: FGF10 requirement for limb initiation and outgrowth.

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