The role of deiodinases in amphibian metamorphosis.

Valerie Galton's prediction over 40 years ago that deiodinases would be important in amphibian metamorphosis has been confirmed. Expression of iodothyronine deiodinase type 2 (D2) and type 3 (D3) occurs in embryogenesis at relevant locations long before the thyroid gland has developed. The expression of D2, an enzyme that synthesizes the active hormone triiodothyronine (T3) from its circulating precursor thyroxine (T4), accurately marks cells at the time that they undergo thyroid hormone-dependent changes. D2 expression in the anterior pituitary controls the maturation of the negative feed back loop between the pituitary and the thyroid gland. The expression of D3, an enzyme that inactivates the hormone, protects cells from responding to the hormone. Its constitutive expression in the dorsal ciliary marginal zone of the tadpole retina results in asymmetric replication of the ventral retina. This in turn leads to ipsilateral projections at the climax of metamorphosis as the frog develops over lapping visual fields. The genes encoding D2 and D3 appear to function in a cell autonomous manner affecting just the cells in which they are expressed. Localized deiodinases represent one of the simplest and most elegant methods to control gene expression, by regulating local concentration of the active hormone in specific cells.