Role of thyroid hormone and retinoid receptors in the homeotic transformation of tails into limbs in frogs.
We provide here further data on the dramatic homeotic transformation of tails into limbs which is induced by retinoids during frog tadpole tail regeneration. The effect can still be produced up to nine days after tail amputation by which time tail regeneration has essentially been completed. Complete tail amputation is needed for the effects to be manifest, partial damage of various sorts to the tail is not enough. We show that as well as retinyl palmitate, other retinoids such as all-trans-retinoic acid and TTNPB, which is a RAR specific retinoid, can induce the homeotic transformation. TTNPB has a 300 x greater potency than retinoic acid. Prolactin, which inhibits thyroid hormone production, prevents the appearance of limbs on the tail from which we conclude that thyroid hormone is needed. We present preliminary evidence from RT-PCR that all six retinoid receptors, the three retinoic acid receptors (RARs), and the three retinoid X receptors (RXRs), are present in the normal tail blastema and that after retinoid treatment RAR alpha, RXR alpha, and RXR beta may be up-regulated. Finally, we show that when RA synthesis is inhibited, normal tail regeneration is inhibited. We conclude that tail regeneration depends upon a particular endogenous level of RA, but that when this level is raised by external administration and thyroid hormone receptors are present the up-regulation of certain retinoid receptors allows novel nuclear receptor interactions which results in the induction of limb-specific genes leading to the appearance of limbs on the tail.
Maden
M
M
Developmental Biology Research Centre, Division of Biomedical Sciences, King's College London, United Kingdom.
Corcoran
J
J
D000671:Amputation, Surgical; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D017931:DNA Primers; D004625:Embryo, Nonmammalian / Q000502:physiology*; D005121:Extremities / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D016133:Polymerase Chain Reaction; D011896:Rana temporaria; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis*; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D047488:Retinoid X Receptors; D012176:Retinoids / Q000494:pharmacology*; D013623:Tail / Q000196:embryology; D014157:Transcription Factors / Q000096:biosynthesis*; D014212:Tretinoin / Q000494:pharmacology*
D001565:Benzoates; D017931:DNA Primers; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; D014212:Tretinoin; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid