Which axis is controlled by the ZPA during limb development?
Vertebrate limb has three orthogonal axes regulated by distinct organizers acting simultaneously. Apical ectodermal ridge with FGFs governs proximal-distal outgrowth and progressive specification via Meis and Hox clock, Wnt7a and Engrailed-1 regulate dorsal-ventral polarity via Lmx1b induction, while zone of polarizing activity at posterior margin secretes SHH establishing anterior-posterior polarity and digit number through Gli3 processing. SHH concentration and duration impart posterior values, highest posteriorly forming digit five. Grafting ZPA anteriorly duplicates digits in mirror image.
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: ZPA controls anterior-posterior axis via SHH.
