PRECOCIOUS SYNTHESIS OF A THYROID-HORMONE RECEPTOR IN XENOPUS EMBRYOS CAUSES HORMONE-DEPENDENT DEVELOPMENTAL ABNORMALITIES

We have investigated the effects of a Xenopus alpha thyroid hormone receptor (TR) upon early development of X. laevis. After deleting the 5'-untranslated region of a cloned TR cDNA, we synthesised TR transcripts that can be translated in oocytes and embryos. When embryos are supplied with this RNA by direct injection, functional TR can be detected through gastrula and neurula stage embryos, considerably in advance of the normal onset of TR expression in larval development. TR mRNA-injected embryos are precociously responsive to thyroid hormone (T3). In the absence of T3 such embryos develop completely normally, but addition of T3 to the medium bathing the embryos results in abnormal embryos with graded anterior (head) deficiencies, losing forehead, eyes and cement gland. progressively. The degree of abnormality is dependent upon the dose of T3 and the stage of development at which it is applied, embryos treated at stage 6 (32 cell) becoming more abnormal than those treated at stage 12 1/2 (late gastrula). Embryos injected with TR mRNA and treated with T3 are similar, but not identical, to embryos treated with retinoic acid in early development. As is the case with retinoic acid treatment, we show that the T3-dependent effects are due, at least in part, to effects on gastrulation movements.