BOTH THYROID-HORMONE AND 9-CIS RETINOIC ACID RECEPTORS ARE REQUIRED TO EFFICIENTLY MEDIATE THE EFFECTS OF THYROID-HORMONE ON EMBRYONIC-DEVELOPMENT AND SPECIFIC GENE-REGULATION IN XENOPUS-LAEVIS
M. Puzianowskakuznicka et al., BOTH THYROID-HORMONE AND 9-CIS RETINOIC ACID RECEPTORS ARE REQUIRED TO EFFICIENTLY MEDIATE THE EFFECTS OF THYROID-HORMONE ON EMBRYONIC-DEVELOPMENT AND SPECIFIC GENE-REGULATION IN XENOPUS-LAEVIS, Molecular and cellular biology, 17(8), 1997, pp. 4738-4749
Tissue culture transfection and in vitro biochemical studies have sugg
ested that heterodimers of thyroid hormone receptors (TRs) and 9-cis r
etinoic acid receptors (RXRs) are the likely in vivo complexes that me
diate the biological effects of thyroid hormone, 3,5,3'-triiodothyroni
ne (T-3). However, direct in vivo evidence for such a hypothesis has b
een lacking. We have previously reported a close correlation between t
he coordinated expression of TR and RXR genes and tissue-dependent tem
poral regulation of organ transformations during Xenopus laevis metamo
rphosis. By introducing TRs and RXRs either individually or together i
nto developing Xenopus embryos, we demonstrate here that RXRs are crit
ical for the developmental function of TRs, Precocious expression of T
Rs and RXRs together but not individually leads to drastic, distinct e
mbryonic abnormalities, depending upon the presence or absence of T-3,
and these developmental effects require the same receptor domains as
those required for transcriptional regulation by TR-RXR heterodimers.
More importantly, the overexpressed TR-RXR heterodimers faithfully reg
ulate endogenous T-3 response genes that are normally regulated by T-3
only during metamorphosis. That is, they repress the genes in the abs
ence of T-3 and activate them in the presence of the hormone. On the o
ther hand, the receptors have no effect on a retinoic acid (RA) respon
se gene. Thus, RA- and T-3 receptor-mediated teratogenic effects in Xe
nopus embryos occur through distinct molecular pathways, even though t
he resulting phenotypes have similarities.