Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2002 Sep 17;9919:12230-5. doi: 10.1073/pnas.182430599.
Show Gene links
Show Anatomy links
Multiple thyroid hormone-induced muscle growth and death programs during metamorphosis in Xenopus laevis.
Das B
,
Schreiber AM
,
Huang H
,
Brown DD
.
???displayArticle.abstract???
Xenopus laevis tadpole tails contain fast muscle fibers oriented in chevrons and two pairs of slow muscle "cords" along the length of the tail. When tail resorption is inhibited by a number of different treatments, fast muscle but not the slow cord muscle still is lost, demonstrating that the fast tailmuscle is a direct target of the thyroid hormone-induced death program. Expression of a dominant negative form of the thyroid hormone receptor (TRDNalpha) was restricted to tadpolemuscle by means of a muscle-specific promoter. Even though the transgene protects fast tailmuscle from thyroid hormone (TH)-induced death, the tail shortens, and the distalmuscle chevrons at the tail tip are degraded. This default pathway for muscle death is probably caused by the action of proteolytic enzymes secreted by neighboring fibroblasts. Non-muscle tissues that are sensitive to TH, such as the fibroblasts, are not protected by the transgene when it is expressed solely in muscle. If allowed to develop to metamorphosis, these transgenic animals die at the climax of metamorphosis before tail resorption has begun. Their limbs have very little muscle even though the rest of limb morphology is normal. Thus, fast tailmuscle and limbmuscle have their own cell autonomous death and growth programs, respectively, that are independent of the fate of the other neighboring cell types. In contrast, death of the slow muscle is controlled by the other cell types of the tail.
Fig 1. The expression profile of tadpoles transgenic for pCar/GFP. (a) Ventral view of the head region of a 1-wk-old tadpole expressing GFP in cardiac and skeletal muscle. (b) GFP expression in the muscle of the developing limb at NF stage 54. (c) GFP expression in the limbmuscle of a juvenile frog. (d) GFP expression in muscle fibers in the middle of the tail region of a stage 57 tadpole. (e) GFP expression in the mid-tail region of a stage 63 tadpole, demonstrating the loss of GFP fibers in the fast muscle chevrons. (f) GFP expression in the slow muscle cords of the tail in a stage 64 tadpole. (g) Loss of GFP-labeled muscle fibers in the tail of a stage 63 tadpole. [Bars = 500 μm (a, b, and f) and 1 mm (c–e and g).]
Fig 2. Assaying muscle loss by using a muscle-specific antibody (MF20) after the 2-wk assay of tadpoles with TH. (a) Tail of an animal treated with 10 nM T3 for 7 days. Note the loss of muscle fibers and disorganization of the chevron structures. (b) Tail of an untreated animal. (c) Tail of a pCar/TRDNα transgenic animal treated with 10 nM T3 for 7 days. (d–f) In situ hybridization of tail cross sections obtained from animals in a–c, respectively, with collagenase-3 antisense probe. (g–i) Changes in the head of the animals in a–c, respectively, after the 2-wk assay. [Bars = 500 μm (a–c and g–i), 100 μm (d and e), and 50 μm (f).]
Fig 3. Caspase-3 activity in the tadpole tails in the 2-wk assay and retention of muscle in tail tip. (a) Tail from a wild-type animal treated with 10 nM T3 for 4 days. Note the caspase-3-positive muscle fibers (examples are shown with arrowheads). (b) Tail from an untreated control animal. (c) Tail from a pCar/TRDNα-expressing animal treated with 10 nM T3 for 4 days. Note the caspase-3-positive epidermal cells similar to a but the lack of caspase-positive muscle fibers. (d–f) Tips of the tail stained with MF20 (red) and anti-active caspase-3 antibody (green) of 10 nM T3-treated (7 days) wild-type, untreated wild-type, and 10 nM T3-treated (7 days) pCar/TRDNα tadpoles, respectively. [Bars = 100 μm (a–c) and 200 μm (d–f).]
Fig 4. Inhibition of activation of caspase-3 in tailmuscle during spontaneous metamorphosis. (a) Cross section through the mid tail region of a wild-type tadpole at NF stage 62 stained with active caspase-3 antibody (red) and MF20 (green) and counterstained with 4′,6-diamidino-2-phenylindole (DAPI; blue). (b) Similarly stained cross section through the mid-tail region of a pCar/TRDNα tadpole. (Bars = 100 μm.)
Fig 5. Inhibition of muscle formation in the limbs in the pCar/TRDNα animal. (a) Wild-type and pCar/TRDNα tadpoles at stage 63. The transgenic animal will die at this stage. (b) The skinned hind limbs of the animals shown in a, demonstrating the reduced muscle formation in the transgenic tadpole. (c) Bone (red) and cartilage (blue) staining of the same hind limbs. [Bars = 1 cm (a) and 500 μm (b and c).]
Berry,
The expression pattern of thyroid hormone response genes in the tadpole tail identifies multiple resorption programs.
1998, Pubmed,
Xenbase
Berry,
The expression pattern of thyroid hormone response genes in the tadpole tail identifies multiple resorption programs.
1998,
Pubmed
,
Xenbase
Brown,
The thyroid hormone-induced tail resorption program during Xenopus laevis metamorphosis.
1996,
Pubmed
,
Xenbase
Buckbinder,
Thyroid hormone-induced gene expression changes in the developing frog limb.
1992,
Pubmed
,
Xenbase
Eliceiri,
Quantitation of endogenous thyroid hormone receptors alpha and beta during embryogenesis and metamorphosis in Xenopus laevis.
1994,
Pubmed
,
Xenbase
Elinson,
Novel structural elements identified during tail resorption in Xenopus laevis metamorphosis: lessons from tailed frogs.
1999,
Pubmed
,
Xenbase
Forrest,
Requirement for the C-terminal domain of the v-erbA oncogene protein for biological function and transcriptional repression.
1990,
Pubmed
Fox,
Degeneration of the tail notochord of Rana temporaria at metamorphic climax. Examination by electron microscopy.
1973,
Pubmed
GROSS,
Collagenolytic activity in amphibian tissues: a tissue culture assay.
1962,
Pubmed
Huang,
Metamorphosis is inhibited in transgenic Xenopus laevis tadpoles that overexpress type III deiodinase.
1999,
Pubmed
,
Xenbase
Huang,
Prolactin is not a juvenile hormone in Xenopus laevis metamorphosis.
2000,
Pubmed
,
Xenbase
Ishizuya-Oka,
Anteroposterior gradient of epithelial transformation during amphibian intestinal remodeling: immunohistochemical detection of intestinal fatty acid-binding protein.
1997,
Pubmed
,
Xenbase
Kerr,
An electron-microscope study of cell deletion in the anuran tadpole tail during spontaneous metamorphosis with special reference to apoptosis of striated muscle fibers.
1974,
Pubmed
Kim,
Autophagy, cytoplasm-to-vacuole targeting pathway, and pexophagy in yeast and mammalian cells.
2000,
Pubmed
Kroll,
Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation.
1996,
Pubmed
,
Xenbase
Lee,
Steroid regulation of autophagic programmed cell death during development.
2001,
Pubmed
Mohun,
Upstream sequences required for tissue-specific activation of the cardiac actin gene in Xenopus laevis embryos.
1986,
Pubmed
,
Xenbase
Nakajima,
Structure, expression, and function of the Xenopus laevis caspase family.
2000,
Pubmed
,
Xenbase
Nishikawa,
Isoform transition of contractile proteins related to muscle remodeling with an axial gradient during metamorphosis in Xenopus laevis.
1994,
Pubmed
,
Xenbase
Nishikawa,
Spatial, temporal and hormonal regulation of programmed muscle cell death during metamorphosis of the frog Xenopus laevis.
1995,
Pubmed
,
Xenbase
Sachs,
Tail regression, apoptosis and thyroid hormone regulation of myosin heavy chain isoforms in Xenopus tadpoles.
1997,
Pubmed
,
Xenbase
Sap,
The c-erb-A protein is a high-affinity receptor for thyroid hormone.
,
Pubmed
Schreiber,
Diverse developmental programs of Xenopus laevis metamorphosis are inhibited by a dominant negative thyroid hormone receptor.
2001,
Pubmed
,
Xenbase
Shibota,
Larval-to-adult conversion of a myogenic system in the frog, Xenopus laevis, by larval-type myoblast-specific control of cell division, cell differentiation, and programmed cell death by triiodo-L-thyronine.
2000,
Pubmed
,
Xenbase
Tata,
Prolactin inhibits both thyroid hormone-induced morphogenesis and cell death in cultured amphibian larval tissues.
1991,
Pubmed
,
Xenbase
Vander Heiden,
Bcl-xL prevents cell death following growth factor withdrawal by facilitating mitochondrial ATP/ADP exchange.
1999,
Pubmed
WEBER,
ULTRASTRUCTURAL CHANGES IN REGRESSING TAIL MUSCLES OF XENOPUS LARVAE AT METAMORPHOSIS.
1964,
Pubmed
,
Xenbase
Wang,
Thyroid hormone-induced gene expression program for amphibian tail resorption.
1993,
Pubmed
,
Xenbase
Weinberger,
The c-erb-A gene encodes a thyroid hormone receptor.
,
Pubmed
Yaoita,
Xenopus laevis alpha and beta thyroid hormone receptors.
1990,
Pubmed
,
Xenbase
Yaoita,
A correlation of thyroid hormone receptor gene expression with amphibian metamorphosis.
1990,
Pubmed
,
Xenbase
Yaoita,
Induction of apoptosis and CPP32 expression by thyroid hormone in a myoblastic cell line derived from tadpole tail.
1997,
Pubmed
,
Xenbase