THE EXPRESSION PATTERN OF THYROID-HORMONE RESPONSE GENES IN THE TADPOLE TAIL IDENTIFIES MULTIPLE RESORPTION PROGRAMS

Expression of genes up-regulated by thyroid hormone (TH) during amphib ian tail resorption was localized by in situ hybridization. The consti tutive thyroid hormone receptor (TR alpha) and its heterodimeric partn ers (RXR alpha and RXR beta) are expressed ubiquitously in the resorbi ng tail. A group of early response genes, including those encoding tra nscription factors, are expressed at greatest levels within tissues wh ose cells attempt to grow and differentiate in the tail, but eventuall y succumb to the resorption program. The TH-inducible TR isoform, TRP, is expressed ubiquitously in the tail, but especially high in fibrobl asts. Similarly, a group of delayed response genes including two prote olytic enzymes that appear to execute the tail resorption program, is expressed specifically in fibroblasts that line and surround the notoc hord and lie beneath the epidermal lamella (subepidermal fibroblasts). During active tail resorption these fibroblasts invade their neighbor ing epidermal and notochord lamellae as part of the resorption process . Expression analysis implicates the single layer of invasive subepide rmal fibroblasts as crucial in tail resorption. Stromelysin-3 is up-re gulated by TH with early kinetics, and is expressed most actively in f ibroblasts within the tail fins. None of the proteases are expressed i n the tadpole epidermis, which will be replaced entirely during metamo rphosis. While very few TH response genes are expressed in tadpole mus cle, many are activated in fibroblasts that surround muscle and could induce muscle cell death by proteolysis of the extracellular matrix. T hese distinct localization patterns suggest that the common fate of al l cell types within the tail is the result of multiple genetic program s. (C) 1998 Academic Press.