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Question

High levels of retinoic acid will convert a distal limb blastema to:

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Explanation

High levels of retinoic acid convert normally distal blastema fate to proximal by transcriptional reprogramming. RA via RAR-RXR binds enhancers of Meis1, Meis2, proximal Hox genes and upregulates glycosylated Prod1 isoform characteristic of proximal cells, while downregulating distal markers HoxA13. Consequently distal amputation plane that would regenerate only hand now regenerates complete arm including stylopod and zeugopod, producing proximalized duplicated limb. Dose-response experiments demonstrate progression: moderate RA duplicates forearm, high duplicates entire arm. This proximalizing effect underlies complete limb regeneration from distal blastema after exogenous retinoid exposure.

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