Meeting Abstract

P1.156  Saturday, Jan. 4 15:30  Doxycycline inhibits organ resorption, but not organ growth, in metamorphosing Xenopus laevis tadpoles CHAVEZ, A; NOLAN, K*; HORN, R; MILLER, B; SCHREIBER, A.M.; St. Lawrence University, NY; St. Lawrence University, NY; St. Lawrence University, NY; St. Lawrence University, NY; St. Lawrence University, NY aschreiber@stlawu.edu

Xenopus laevis metamorphosis is characterized by the complete resorption of some tadpole-specific organs (tail and gills), the growth and differentiation of adult-specific organs (limbs), and the remodeling of other organs from a tadpole to a frog form (brain, gut). Virtually all of these different developmental programs of metamorphosis are mediated by thyroid hormone (TH). Matrixmetalloproteases (MMPs) are enzymes that remodel the extracellular matrix and facilitate changes in organ shape. The mRNAs of several amphibian MMPs are known to be upregulated directly (i.e. stromelysin-3) or indirectly (e.g. gelatinase A and MT1-MMP) by TH. Although MMP mRNAs are known to be upregulated in diverse tissues during metamorphosis, the actual roles of MMP activity in these tissues remain unclear. To determine the influence of MMP activity on diverse developmental programs of metamorphosis, we raised Nieuwkoop-Faber stage 50 tadpoles in the presence of the broad-spectrum MMP inhibitor, doxycycline (DOXY, 65 ug/ml) for 7 days in the presence or absence of TH (5 nM T3). Treatment of tadpoles with TH alone induced multiple metamorphic programs, including the shortening and cross-sectional remodeling of the gut, gill resorption, tail resorption, brain thickening (due to cell proliferation), and growth of the limbuds. Treatment of tadpoles concurrently with TH+DOXY had no effect on limb or brain growth, but did significantly inhibit gut remodeling and resorption of both the gills and tail. These findings suggest that MMP activity plays an important role in organ resorption and remodeling, but is less prominent in organ growth.