A hypothesis for the transcriptional control of amphibian metamorphosis by the thyroid hormone receptor

Abstract

SYNOPSIS. Amphibian metamorphosis is controlled by thyroid hormone and the thyroid hormone receptor. The thyroid hormone receptor functions as a master control factor that can both activate and repress genes in controlling the transformation of the larval tadpole to the adult frog. We have made use of the microinjection of both Xenopus laevis oocytes and embryos to investigate the molecular mechanisms involved in this regulation of transcription. We define three steps in the regulation of transcription by thyroid hormone receptor: the establishment of a repressive chromatin structure, disruption of chromatin and transcriptional activation. Our results also suggest that there are four major stages in the developmental control of gene expression during metamorphosis 1) Tissue and stage specific expression during embryonic development prior to tadpole hatching independent of thyroid hormone receptor. 2) The general repression of transcription of these genes by thyroid hormone receptor after tadpole hatching (stage 36), but prior to the production of thyroid hormone, which is first detectable in the circulating plasma around stage 55. 3) The activation of transcription dependent on thyroid hormone and receptor at metamorphosis (stages 55-66). 4) The acquisition of tissue specific and possibly thyroid hormone-independent patterns of gene activity.