Which signaling molecule is required for AER maintenance and limb bud outgrowth?
Sustained limb outgrowth requires continuous FGF8 from apical ectodermal ridge acting on distal mesenchyme. FGF8 activates ERK MAPK and AKT pathways maintaining expression of FGF10, Gremlin and Msx2 in progress zone, preserving proliferation, preventing premature differentiation, and enabling progressive distal specification through Hox activation. Genetic ablation of Fgf8 in mouse AER causes hypoplastic limbs lacking distal elements but forming stylopod proximally. Replacement with FGF8-soaked beads rescues after AER removal, restoring outgrowth and skeletal pattern. Wnt3a induces AER initially, FGF10 induces FGF8, RA antagonizes FGF.
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: FGF8 requirement for AER maintenance.