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#limb bud formation

2 public questions tagged with this topic.

Limb Development -ll

Which transcription factor regulates EMT during limb bud formation?

Epithelial-mesenchymal transition enabling lateral plate accumulation into limb bud is regulated by TBX5 and Islet1 cofactor complexes forming transcriptional hubs. These T-box factors repress epithelial E-cadherin and tight junction programs, induce Snail Slug to permit delamination, increased motility and aggregation of limb field progenitors into protruding bud with elevated FGF10. Wnt3a signals via beta-catenin to induce AER but not direct EMT execution, Islet1 cooperates via Ldb1 rather than sole driver, SHH acts later in patterning. TBX5 therefore functions not only in specification but also controlling EMT and progenitor recruitment for bud morphogenesis.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: TBX5 regulates EMT during limb bud formation.

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Limb Development -ll

Which experiment demonstrated that mesodermal signals induce limb bud formation?

Proof that mesodermal FGF10 initiates limb budding came from gain-of-function implantation experiments. Implanting FGF10-soaked heparin beads beneath flank ectoderm of chick embryos outside normal limb fields induced ectopic Wnt3a, beta-catenin activation and AER formation expressing FGF8, followed by complete extra limb containing stylopod zeugopod autopod and digits with muscle and cartilage. Conversely, AER removal causes truncation, TBX5 knockout prevents forelimb, AER graft from another species still supports outgrowth due to permissive nature. Thus FGF10 bead experiment proved mesodermal signals sufficient to induce full limb formation program de novo.

Ref: Ohuchi et al., Development 1997, Gilbert Chapter 20: Ectopic FGF10 induces additional limbs.

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