Practice question

Maintenance of ZPA depends on distal FGF signals through SHH-Gremlin-FGF epithelial-mesenchymal loop. Classic bead experiments placed FGF8-soaked heparin acrylic beads near posterior mesenchyme after AER removal or in anterior grafts, demonstrating prolonged SHH expression and preservation of Gremlin domain and continued proliferation. Without FGF, SHH decays rapidly and digits truncate anteriorly. BMP inhibition reduces interdigital death but does not sustain SHH. Gremlin removal accelerates BMP-mediated AER loss, Hox overexpression alters proximal-distal identity. Therefore FGF8 bead experiments directly proved AER-derived FGFs maintain ZPA SHH expression and AP patterning.