THE MOLECULAR-BASIS OF THYROID HORMONE-DEPENDENT CENTRAL-NERVOUS-SYSTEM REMODELING DURING AMPHIBIAN METAMORPHOSIS

Tadpole metamorphosis involves a coordinated series of changes in virt ually every tissue of the body. This developmental process is induced by the single morphogen, thyroid hormone (TH). The amphibian central n ervous system (CNS) is a primary target for TH, and it undergoes drama tic morphological and cytoarchitectural changes in response to the hor mone. TH acts by regulating gene expression and its actions in metamor phosis are thought to result from its ability to induce tissue-specifi c genetic programs. Receptors for TH are ligand-dependent transcriptio n factors whose mRNA expression is upregulated by TH during metamorpho sis (receptor autoinduction). Studies on the tadpole CNS have identifi ed four general classes of early TH response genes. These genes code f or: (1) transcription factors, that are likely to be required for the expression of downstream genes (i.e. secondary response genes), (2) ce llular enzymes, which carry out hormone conversions, energy transforma tions and may possibly mediate extranuclear effects of TH on neural ce lls, (3) cytoskeletal elements required for axonal development, and (4 ) secreted signaling molecules that control the production of TH. Rece nt studies suggest a critical, evolutionarily conserved role for the T H-induced transcription factor genes in controling neural cell prolife ration and differentiation. (C) 1998 Elsevier Science Inc. All rights reserved.