How hormones regulate programmed cell death during amphibian metamorphosis

Extensive programmed cell death is initiated at the onset of amphibian metamorphosis, resulting in 100% of cells dying in some larval tissues, as during total regression of tail and gills. All cell death during metamorphosis is under the control of thyroid hormone (TH), which can initiate the process precociously in whole tadpoles, or in individual tissues in culture. The hormone prolactin (PRL), given exogenously, prevents natural and TH-induced metamorphosis. We have exploited this dual hormonal regulation in premetamorphic Xenopus tails in organ culture to identify and characterize ''early'' genes that are TH-induced and considered important for initiating cell death. Among the earliest genes activated by TH is that encoding the thyroid hormone receptor TRP. This autoinduction of TR genes is considered important since, in blocking this process, PRL also inhibited the expression of other TH-inducible genes and prevented cell death. The expression of ''early'' genes other than TR genes, that are known to promote cell death (e.g. nur-77 and ICE) or survival (e.g. Xenopus bcl-2-like genes), is also considered to be important for the initiation of programmed cell death during amphibian metamorphosis. The possible significance of thyroid hormone-mediated amphibian metamorphosis to mammalian fetal development will be briefly discussed.