Practice question

Hindlimb developmental program hierarchy places Pitx1 at top of caudal limb field upstream of Tbx4 and FGF10 controlling identity. Pitx1 activates Tbx4 enhancer and directly regulates hindlimb-specific enhancers of FGF10 and Hoxc10 genes controlling hindlimb morphology and muscle patterning. Tbx4 then maintains FGF10 levels and activates hindlimb differentiation, while Islet1 cooperates to maintain Pitx1 expression via shared enhancer inputs and Ldb complex. Wnt3a primarily induces forelimb field via beta-catenin activation, TBX4 downstream of Pitx1, Islet1 parallel but cooperative. Therefore PITX1 functions genetically upstream of FGF10 in hindlimb development.