What is the primary function of the Zone of Polarizing Activity (ZPA)?
Zone of polarizing activity is posterior mesenchymal signaling center secreting Sonic hedgehog morphogen. SHH diffuses anteriorly establishing concentration gradient that regulates Gli3 processing from activator to repressor form, thereby specifying digit number and identity. High posterior concentration induces digits 4-5 via Hand2 and posterior HoxD targets, low anterior allows digit 1. Grafting ZPA anteriorly induces mirror-image duplication. Conditional Shh deletion causes loss of posterior digits and reduced proliferation. ZPA also maintains AER via Gremlin-mediated BMP inhibition, integrating growth and patterning.
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: ZPA, SHH gradient, and anterior-posterior patterning.