Patuxent Wildlife Research Center
NAAMP III Archive - deformed frogs
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Patuxent
Wildlife Research Center
NAAMP III Archive
- deformed frogs
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by Alphabetical Order | Archive by Category
Tulane University.
The discovery of adult frogs harboring gross limb deformities ranging from the absence of limbs to the formation of multiple additional limbs indicates an environmental disruption of limbdevelopment. While frog limb development has not been specifically studied, vertebrate limbdevelopment has been the focus of intense investigation with the mouse, chicken, andsalamander limbs as models. Among vertebrates the developmental anatomy, the molecularcharacteristics, and in some cases, direct experimentation indicates that all vertebrate limbsdevelop in a similar manner. Of the types of limb deformities displayed by frogs caught in thewild, the formation of multiple limbs, called supernumerary limbs, is the most informative. Theformation of supernumerary limbs in laboratory experiments is used as an indicator of signalingpathways important for the initiation of limb formation. Thus far two signaling pathways thatlead to supernumerary limb formation have been identified and partially characterized. The firstinvolves signaling by a family of factors called fibroblast growth factor (FGF). FGF signalinghas been linked to the initiation of bud formation, maintaining bud outgrowth, and the inductionof a regeneration response following bud amputation. FGF signaling has also been linked to theinhibition of limb formation in experiments in which a source of FGF is placed at the base of thelimb bud. FGFs are secreted primarily by ectodermal cells at the apex of the limb bud that forma structure called the Apical Ectodermal Ridge (AER). Signaling occurs via a tyrosine kinase cellsurface receptor (FGF receptor) that is expressed on mesenchyme cells. The biological activitiesof FGF signaling in the limb bud include the stimulation of cell proliferation, the regulation ofcell migration, and the induction of genes known to be important for the control of limboutgrowth. It is possible that an environmental interface with this signaling pathway could leadto limb deformities that include the absence of limbs and the formation of ectopic supernumerarylimbs.
A second pathway important for limb formation involves hormone signaling by retinoic acid(RA). Endogenous RA signaling is important for setting up the limb field prior to outgrowth. Introducing an ectopic source of RA leads to the induction of supernumerary limbs, whereasinhibiting RA synthesis or systemic exposure to high levels of RA can result in the inhibition oflimb outgrowth altogether. RA is a lipophilic signaling molecule that is synthesized from aubiquitous non-signaling precursor, retinol, and functions by activating nuclear receptors that areligand-dependent transcription factors present in responsive cells. The level of RA in the cell isregulated by cytoplasmic retinoic acid bind proteins (CRABP) that function as an intracellularbuffer. Experiments directly on frogs indicate that exogenous RA results in hypomorphic limbdeformities (absence of limb structures), whereas exogenous RA in association with aregeneration response results in a hypermorphic response which includes the duplication ofstructures in the proximal-distal and the formation of supernumerary limbs. In addition,exogenous RA in association with tail regeneration results in a homeotic transformation of tailtissue into limb tissue with the ectopic formation of clusters of supernumerary hindlimbs fromthe wound site. The RA induced supernumerary limbs are morphologically similar to thesupernumerary response observed in deformed frogs caught in the wild. These morphologicalsimilarities raise the possibility that the limb deformities observed in wild frog populations arecaused by chemical pollutants present in the environment that disrupt RA signaling during limbdevelopment. There are multiple ways that the RA signaling pathway could be affected byenvironmental pollutants, including 1) RA signaling mimics, 2) RA antagonists, and 3)modifying levels of CRABP. Evidence that chemical present in the environment can act tomimic retinoid signaling exist from laboratory studies.
U.S. Department of the Interior
U.S. Geological Survey
Patuxent Wildlife Research Center
Laurel, MD, USA 20708-4038
http://www.pwrc.usgs.gov/naamp3/naamp3.html
Contact: Sam Droege, email: Sam_Droege@usgs.gov
Last Modified: June 2002