Meeting Abstract
P1.33 Monday, Jan. 4 Treatment of Xenopus laevis tadpoles with pharmacological inhibitors of matrix-metalloproteases (MMPs) suppresses metamorphic intestinal remodeling MILLER, B.*; SCHREIBER, A.M.; St. Lawrence Univ., Canton NY; St. Lawrence Univ., Canton NY aschreiber@stlawu.edu
During frog metamorphosis the herbivorous tadpole transforms into a carnivorous frog. Tadpole intestinal development is characterized by a 75% shortening of its length, thickening of the muscle and mesenchyme, and the development of extensive luminal folds. All metamorphic changes are mediated by thyroid hormone (TH) and its nuclear receptors that function as gene transcription factors. Several MMPs are up-regulated in the intestine by TH during metamorphosis. However, the actual functions of MMPs in intestinal development remain unclear. We have developed a simple and effective method to pharmacologically inhibit tadpole intestinal MMP activity in vivo, and study the effects of this suppression on subsequent TH-mediated intestinal development. Premetamorphic tadpoles (NF 51) were treated for 2 days with a broad-spectrum MMP inhibitor (doxycycline, 100 ug/ml) added to the water. Intestinal remodeling was then induced by adding 3 nM triiodothyronine (T3) to the water in the presence or absence of MMP inhibitor for 4 days. Gut lengths were measured, and gut cross-sections were analyzed histologically. Gut lengths of tadpoles treated with MMP inhibitor only (9.6±0.2 mm) were not different than for untreated tadpoles (9.3±0.3 mm). Gut lengths of tadpoles treated with T3 only (6.7±0.2 mm) were significantly shorter compared with untreated animals. However, guts of tadpoles treated with MMP inhibitor+T3 failed to shorten, with lengths (8.9±0.3 mm) not significantly different compared with untreated animals. Whereas treatment with T3 only produced a constricted intestinal cross-section and thickening of the mesenchyme compared with untreated tadpoles, gut cross-sections of animals treated with T3+MMP inhibitor were similar to those of untreated tadpoles.
