Thyroid hormones and their nuclear receptors: new players in intestinal epithelium stem cell biology?
Amphibian metamorphosis involves systematic transformations of various tadpole organs/tissues. Three major types of changes take place during this process. These are remodeling, resorption, and de novo development, all of which appear to involve both cell proliferation and apoptosis (programmed cell death). All metamorphic changes are controlled by thyroid hormone (T3) and are organ-autonomous. Recent studies using primary cell cultures and a stably transformed cell line from tadpole tissues have implicated that T3 induces apoptosis cell-autonomously. This T3-induced, metamorphosis-associated apoptosis is similar to cell death in other animal species and involves similar cell death executioners. Both the activation of these executioners and the pathways leading to cell proliferation and differentiation are believed to be through transcriptional regulation by T3 receptors (TRs). TRs can activate or repress target gene transcription depending upon the presence or absence of T3, respectively. Many direct T3-response genes have been isolated and found to encode a variety of proteins that can affect both intra- and extra-cellular events. The determinations of the identities of these response genes through sequence analyses and studies on their expression profiles during development have provided strong clues toward their roles in metamorphosis. However, future studies using organ and cell culture systems and/or transient or stable transgenic technologies are required to understand how these genes transduce the T3 signal to activate the downstream cell death and proliferation/differentiation pathways.