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Deiodinase Activity Is Present in Xenopus laevis during Early Embryogenesis

Department of Regulations, Development, and Molecular Diversity (G.M.D., A.S., B.A.D.), Muséum National d’Histoire Naturelle, 75231 Paris, France; Department of Internal Medicine (G.G.J.M.K., T.J.V.), Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands; Laboratory of Comparative Endocrinology (C.H.J.V., V.M.D.), Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; and Watchfrog SAS (A.S.), c/o Muséum National d’Histoire Naturelle, 75321 Paris, France

Address all correspondence and requests for reprints to: Professor Barbara Demeneix, Unité Mixte de Recherche Centre National de la Recherche Scientifique 5166, Evolution des Régulations Endocriniennes, Department of Regulations, Development, and Molecular Diversity, Museum National d’Histoire Naturelle, 7 Rue Cuvier, 75231 Paris Cedex 05, France. E-mail: demeneix{at}mnhn.fr.

Thyroid hormones orchestrate amphibian metamorphosis. The type 2 and type 3 deiodinases make vital contributions to this process by controlling levels of the thyroid hormones T₄ and T₃ available to different tissues. Because the tadpole thyroid gland is not functional until stage NF44, it has been widely assumed that thyroid signaling is absent during amphibian early development, thyroid hormone only becoming a major regulator during premetamorphic stages. Similarly, in mammals, thyroid function is known to be essential to neuronal development, especially during the perinatal stages, but again little is known about early stages of development. Here we demonstrate that key elements of thyroid hormone signaling are present during early development of Xenopus. In particular, we find functional thyroid hormone-activating deiodinases and significant levels of their substrates, T₄ and T₃, during early embryogenesis. Furthermore, we have further characterized a recently identified deiodinase in amphibians, homologous to mammalian type 1 deiodinase (D1). This enzyme is expressed in marked, spatially defined patterns during embryogenesis. The patterns of expression of type 1 deiodinase are distinct from those of type 2 and type 3 deiodinases. Deiodinase expression is found in neurogenic areas from stage NF30 onward, both in the central and peripheral nervous systems. We conclude that both activating and inactivating deiodinases show dynamic patterns of expression during early embryogenesis in amphibians, particularly in neurogenic areas. These findings suggest that thyroid hormone signaling is a key component of early neuronal development in vertebrates.

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