Practice question

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.