One of the most dramatic advances in biomedical research in the past t5 years has been the demonstration that human disorders can be studied in model organisms. This is a tribute to the investment of our country in basic biology. Genetic organisms such as yeast, Drosophila, C. etegans, and the mouse have led the way, but the organism par excellence for the study of thyroid hormone, one of the most important hormones for human health, is the amphibian, Xenopus laevis. Although vertebrates in all of the various phyla including humans require thyroid hormone (TH) to complete their life cycle, by far the most dramatic example is the role of TH in amphibian metamorphosis. TH is required absolutely for all of the remarkable changes that convert a tadpole into a frog. Many features of TH biology are identical in all vertebrates. However, the ease with which the model amphibian organism, X. laevis can be raised in the laboratory, the ability to manipulate TH levels, and the abundance of the material all make X. laevis the best model organism to study the action of TH. The mere addition of TH to the rearing water induces all of the events of metamorphosis. TH controls celt death, cell proliferation, and the remodeling of organs. Modem genetic methods are being applied to X. laevis with great success beginning with the new sperm mediated transgenesis technique of Kroll and Amaya. By expressing genes or mutant genes that interfere with metamorphosis in specific cell types the TH-controtled developmental program of a single cell type can be inhibited or activated selectively. The expression of detrimental gene products can be activated in cells at precise times in development utilizing controllable promoters. This wonderful old biological problem that previously could only be described by scientists is now yielding to modem molecular methods.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM022395-32S1
Application #
7600738
Study Section
Special Emphasis Panel (ZRG1-DEV-1 (01))
Program Officer
Haynes, Susan R
Project Start
1975-09-01
Project End
2010-03-31
Budget Start
2007-04-01
Budget End
2010-03-31
Support Year
32
Fiscal Year
2008
Total Cost
$78,000
Indirect Cost
Name
Carnegie Institution of Washington, D.C.
Department
Type
DUNS #
072641707
City
Washington
State
DC
Country
United States
Zip Code
20005
Mukhi, Sandeep; Brown, Donald D (2011) Transdifferentiation of tadpole pancreatic acinar cells to duct cells mediated by Notch and stromelysin-3. Dev Biol 351:311-7
Pearl, Esther J; Bilogan, Cassandra K; Mukhi, Sandeep et al. (2009) Xenopus pancreas development. Dev Dyn 238:1271-86
Brown, Donald D; Cai, Liquan (2007) Amphibian metamorphosis. Dev Biol 306:20-33
Cai, Liquan; Das, Biswajit; Brown, Donald D (2007) Changing a limb muscle growth program into a resorption program. Dev Biol 304:260-71
Furlow, J D; Brown, D D (1999) In vitro and in vivo analysis of the regulation of a transcription factor gene by thyroid hormone during Xenopus laevis metamorphosis. Mol Endocrinol 13:2076-89
Wolffe, A P; Brown, D D (1988) Developmental regulation of two 5S ribosomal RNA genes. Science 241:1626-32
Setzer, D R; Brown, D D (1985) Formation and stability of the 5 S RNA transcription complex. J Biol Chem 260:2483-92
Brown, D D; Schlissel, M S (1985) The molecular basis of differential gene expression of two 5S RNA genes. Cold Spring Harb Symp Quant Biol 50:549-53