Effects of retinoic acid on limb bud pattern formation and limb blastema pattern formation

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To examine common mechanisms of Retinoic acid (RA)-induced pattern formation in the developing limb bud and regenerating limb blastema, chick limb bud at satge 20 was treated with RA for 10 hours by implanting RA-bead and then the mesenchymal tissue near the bead was transplanted to the anterior margin of otherlimb bud at stage 18-19. The RA-treated and transplanted tissues formed all the cartilage elements from humerus to degits, although the control transplants formed only digits according to their fate. This "proximalization" occurred independently of posteriorization, that is, induction of ZPA.The expression pattern of HoxA, which was known to change corresponding to the proximodistal positional value in normal limb development, changed to show the proximalization in RA-treated transplants. The cell affinity also changes according to the positional values. The dissociated cells of RA-treated mesenchyme showed the proximalization to segregate from those of untreated tissues in monolayr culture. These results suggest that the cells of RA-treated mesenchyme of developing limb changes their positional value to show proximalization other than posteriorization as shown previously in regeneration blastema of salamander limb.