Meeting Abstract

P1-100  Thursday, Jan. 5 15:30 – 17:30  Matrixmetalloprotease Activity is Required for both Longitudinal and Cross-sectional Intestinal Remodeling during Xenopus laevis Metamorphosis DUDLEY, C*; FOOTE, S; DAVIS, T; HORN, R; MILLER, B; SCHREIBER, AM; St Lawrence University, NY; St Lawrence University, NY; St Lawrence University, NY; St Lawrence University, NY; St Lawrence University, NY; St Lawrence University, NY aschreiber@stlawu.edu

Metamorphosis of the herbivorous tadpole into a carnivorous frog is accompanied by an abrupt remodeling of the gut: the intestine shortens by 75%, the connective tissue and smooth muscle layers thicken, enteric neuronal cell bodies form clusters, and the lumen becomes highly involuted. Virtually all aspects of amphibian metamorphosis are mediated by thyroid hormone (TH), and the mRNAs of several matrixmetalloprotease (MMPs) are known to be upregulated directly (stromelysin-3) or indirectly (gelatinase A and MT1-MMP) in the gut mesenchyme by TH. However, the specific roles of MMP enzymatic activity on intestinal remodeling have not been well-described. Here we show that treatment of pre- and pro-metamorphic tadpoles with a broad-spectrum inhibitor of MMP activity (doxycycline, DOXY) inhibits 25-35% of intestinal MMP activity. Furthermore, in the presence of DOXY, TH treatment failed to induce virtually all aspects of metamorphic intestinal remodeling, including gut shortening, thickening of the mesenchyme and smooth muscle layers, and the development of involutions on the lumen. These findings directly support the hypothesis that an upregulation of TH-responsive MMP activity during metamorphosis mediates diverse changes that accompany intestinal remodeling.