Matrix metalloproteinases mediate the dismantling of mesenchymal structures in the tadpole tail during thyroid hormone‐induced tail resorption

It has been suggested that a family of tissue remodelling enzymes called matrix metalloproteinases (MMPs) play a causal role in the process of tail resorption during thyroid hormone‐induced metamorphosis of the anuran tadpole; however, this hypothesis has never been directly substantiated. We cloned two new Xenopus MMPs, gelatinase A (MMP‐2) and MT3‐MMP (MMP‐16), and the MMP inhibitor TIMP‐2. These clones were used along with several others to perform a comprehensive expression study. We show that all MMPs and TIMP‐2 are dramatically induced in the resorbing tail during spontaneous metamorphosis and are spatially coexpressed, primarily in the remodelling mesenchymal tissues. By Northern blotting, we show that all the examined MMPs/TIMP‐2 are also induced by treatment of organ‐cultured tails with thyroid hormone (T3). Using the organ culture model, we provide the first direct evidence that MMPs are required for T3‐induced tail resorption by showing that a synthetic inhibitor of MMP activity/expression can specifically retard the resorption process. By gelatin zymography, we also show T3 induction of a fifth MMP, preliminarily identified as gelatinase B (GelB; MMP‐9). Moreover, T3 not only induces MMP/TIMP expression but also MMP activation, and we provide evidence that TIMP‐2 participates in the latter process. These findings suggest that MMPs and TIMPs act in concert to effect the dismantling of mesenchymal structures during T3‐induced metamorphic tadpole tail resorption. © 2002 Wiley‐Liss, Inc.