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Question

What is the main role of RA in limb development?

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Explanation

Two opposing gradients establish proximal-distal axis. Retinoic acid synthesized in flank creates proximal environment, inducing Meis1 Meis2 and proximal Hox programs governing stylopod specification. Distal FGF8 from AER induces Cyp26b1, an RA-degrading enzyme, clearing RA distally and permitting distal Hox12-13 activation and Meis repression. Excess RA proximalizes distal structures, RA inhibition distalizes. This two-signal model explains proximal dominance when AER removed early. RA does not directly determine hindlimb identity, prevent autopod apoptosis, or primarily regulate FGF transcription; its core function is imposing proximal character versus distal FGF.