TEMPORAL AND SPATIAL EXPRESSION OF AN INTESTINAL NA+ PO43- COTRANSPORTER CORRELATES WITH EPITHELIAL TRANSFORMATION DURING THYROID HORMONE-DEPENDENT FROG METAMORPHOSIS/

The amphibian intestine has two morphologically distinct structures du ring development. Early embryogenesis generates a simple, tubelike int estine in the tadpole whereas after thyroid hormone (T-3)-dependent me tamorphosis a newly remodeled adult intestine is formed similar to tha t of higher vertebrates. This change requires a drastic transformation of the epithelial layer. We have isolated a Na+/PO43- cotransporter g ene that may contribute to this transformation. The deduced amino acid sequence of this gene shows a high degree of homology to the mammalia n renal Na+/PO43- cotransporters, which have little or no expression i n organs other than the kidney. The frog gene is highly expressed and regulated by T-3 in the intestine with lithe expression and/or regulat ion by T-3 in most other organs. Its mRNA is restricted to the differe ntiated epithelial cells both in tadpoles and postmetamorphic frogs. I nterestingly, its expression is low in premetamorphic tadpoles, but up -regulated when metamorphosis is initiated by endogenous T-3. As the l arval epithelium undergoes programmed cell death (apoptosis), the mRNA level drops to a minimum. Subsequently the gene is reactivated at the tip region of the newly formed adult intestinal folds and a crest-tro ugh polarity of expression is established by the end of metamorphosis. This temporal regulation profile is also reproduced when premetamorph ic tadpoles are treated with T-3 to induce precocious intestinal remod eling. These results suggest a possible role of the Na+/PO43- cotransp orter during metamorphosis and demonstrate that the adult epithelial c ell differentiation pattern is established in the direction of crest-t o-trough of the intestinal fold, concurrent with the epithelial morpho genic process. (C) 1997 Wiley-Liss, Inc.