Hormonal regulation of programmed cell death during amphibian metamorphosis.

Extensive programmed cell death (PCD) 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 are those encoding the two thyroid hormone receptors TR alpha and TR beta. 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, which are known to promote cell death or survival, is also considered to be important for the initiation of PCD during amphibian metamorphosis. We are, therefore, working on the identification, characterization, and expression of members of the Xenopus bcl-2-like gene family, as well as other genes, such as nur-77 and ICE, which may act as early genes during tadpole tail regression.