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#Tbx5

5 public questions tagged with this topic.

Limb Development -l

Which transcription factor is responsible for forelimb specification?

Forelimb versus hindlimb identity is encoded by T-box transcription factors expressed in lateral plate mesoderm before any morphological bud. Tbx5 is restricted to presumptive forelimb field, where it upregulates Fgf10 and Wnt2b and launches forelimb-specific enhancer program leading to arm or wing formation. Tbx4 together with Pitx1 and Islet1 marks hindlimb field and specifies leg development. Genetic ablation of Tbx5 abolishes forelimb initiation entirely, while ectopic Tbx5 expression in flank can induce supernumerary wing-like buds, establishing its master selector status for forelimb.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: Limb identity – Tbx5 forelimb specification and Tbx4/Pitx1.

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Tetrapod

Which transcription factor is responsible for forelimb development in tetrapods?

Forelimb determination depends on T-box transcription factor TBX5 expressed in anterior lateral plate mesoderm rostral to hindlimb region. TBX5 directly activates Fgf10 transcription in forelimb field progenitors, triggering downstream Wnt3a and Fgf8 in ectoderm and establishing self-sustaining outgrowth loop. TBX5 loss-of-function mutations cause Holt-Oram syndrome featuring thumb and radial defects plus cardiac septal anomalies reflecting cardiac co-expression. Homozygous mouse knockout eliminates forelimb bud induction completely while hindlimbs remain normal, proving specific requirement. Ectopic TBX5 can induce additional wing-like bud in interlimb region experimentally.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: TBX5 in forelimb specification and Holt-Oram syndrome.

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