Practice question

Forelimb field is defined by T-box transcription factor TBX5 expressed exclusively in rostral forelimb-forming lateral plate mesoderm downstream of axial Hox4-5 and Wnt2b signals. TBX5 activates FGF10 and Wnt2b enhancers, initiating forelimb bud and AER induction via Wnt3a beta-catenin. TBX4 and Pitx1 perform analogous hindlimb functions caudally with Islet1. Tbx5 knockout mice lack forelimbs entirely while hindlimbs form normally; human TBX5 haploinsufficiency causes Holt-Oram syndrome with thumb anomalies. Lmx1b patterns dorsal compartment, Pitx1 reinforces hindlimb. Therefore forelimb specification depends essentially on TBX5 upstream cascade.