Proximal-distal positional values in limb regeneration are influenced by gradients of:
Proximal-distal positional values determining which segments regenerates are encoded by counter-gradients of retinoic acid proximally and FGFs distally. High RA proximal limb activates Meis1/2 specifying proximal identities, distal FGF8/10 from apical cap promotes HoxA13 distal fate. Blastema cells interpret RA-to-FGF ratio through intracellular receptors regulating Prod1 adhesion molecule gradient and Hox codes. Experimental manipulation: RA treatment proximalizes, excess FGF distalizes. Affinophoresis experiments sorting proximal and distal blastema cells based on differential adhesion corroborate gradient encoding positional memory and intercalary regeneration behavior following positional disparity grafting.
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 21: RA and FGF gradients controlling proximal-distal identity.