Practice question

TBX5 is upstream activator of forelimb bud initiation. It induces FGF10 in lateral plate mesoderm which signals to ectoderm to form AER and express FGF8, establishing reciprocal signaling sustaining proliferation. Homozygous inactivation via Prx1-Cre conditional knockout deletes TBX5 throughout limb field resulting in complete failure of forelimb bud outgrowth, embryos develop with no scapula, humerus or distal elements, while hindlimbs appear normal. Heterozygous humans exhibit Holt-Oram syndrome with thumb hypoplasia and heart defects, highlighting dosage sensitivity and conserved role throughout tetrapods and zebrafish pectoral fins.