Abstract
IN urodele amphibians, the progenitor cells that regenerate amputated limbs (known as the blastema) normally replace only the missing structures1. After systemic delivery of retinoic acid (RA), more proximal structures are also formed, indicating that RA can control position specification in the proximal–distal axis of the regenerating limb2–4. According to dose and experimental context, retinoids can also re-specify the anteroposterior axis of the limb, induce deletions of skeletal elements, or block re-growth completely2, 5–10. To study the molecular basis of these morphogenetic effects, we screened complementary DNA libraries of newt regenerative tissues (limbs and tails) for hormone nuclear receptors activated by RA11–17. Two functional retinoic acid receptors (RARs) were identified, one of which is the newt homologue of the human α-receptor (RARα). The second receptor, called RARδ, is novel. Sequence analysis suggests that the composite newt RAR previously reported18 is chimaeric, consisting of 5'RAR-β-like and 3' RARδclones. We conclude that multiple RARs are expressed during limb regeneration in amphibians and suggest that receptor heterogeneity may underlie the different effects of retinoids on limb morphogenesis.
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Ragsdale, C., Petkovich, M., Gates, P. et al. Identification of a novel retinoic acid receptor in regenerative tissues of the newt. Nature 341, 654–657 (1989). https://doi.org/10.1038/341654a0
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DOI: https://doi.org/10.1038/341654a0
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