Plenary lecture

"How a tadpole turns into a frog"

Donald D. Brown
Carnegie Institution
3520 San Martin Dr.
Baltimore, MD 21218


Amphibian metamorphosis, the development of a tadpole into a frog, is controlled by thyroid hormone (TH). The same two thyroid receptors mediate this response in all of the target tissues. We have prepared transgenic Xenopus laevis in which a dominant negative form of the receptor (TRDN) fused to GFP is driven by a cell-specific promoter. This transgene is controlled by the tetracycline inducible system and therefore can be induced at any time during development of the tadpole. The transgene inhibits the TH-induced metamorphic response in a cell autonomous manner. Applying this to the development of the limb demonstrates that the TH-induced changes in muscle, bone/cartilage, innervation, and skin are independently controlled by TH. Microarray analyses of limb growth and tail resorption clearly show the collection of genes in major functional pathways that are changed in these opposite TH-induced events. In fact the same set of genes is often down-regulated in the tail and up-regulated in the limb.
Supported by a grant from NIH and the G. Harold and Leila Y. Mathers Foundation

Bibliography

Marsh-Armstrong, N,. Cai, L. and Brown, D.D. Thyroid hormone controls the development of connections between the spinal cord and limbs during Xenopus laevis metamorphosis
Proc. Nat. Acad. Sci. 101: 165-170 (2004)

Das, B, and Brown, DD Controlling transgene expression to study Xenopus laevis metamorphosis. Proc. Nat. Acad. Sci. 101: 4839-4842. (2004).

Schreiber, AM and Brown, DD. Remodeling of the intestine during metamorphosis of Xenopus laevis. Proc. Nat. Acad. Sci 102: 3720-3725 (2005).

Brown, DD, Cai, L, Das, B, Marsh-Armstrong, N, Schreiber, AM, and Juste, R. Thyroid hormone controls multiple independent programs required for limb development in Xenopus laevis metamorphosis. Proc. Nat. Acad. Sci. 102: 12455-12458 (2005).

Das, B, Cai, L, Carter, MG, Piao, Y-L, Sharov, AA, Ko, MSH, Brown, DD. Gene expression changes at metamorphosis induced by thyroid hormone in Xenopus laevis tadpoles. Dev. Biol. (2006) in press.

共催：広島大学　21世紀ＣＯＥプログ ラム
      放射線災害医療開発の先端的研究教育拠点
      −ゲノム障害科学に基づく学術基盤の確立と医療展開−

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