There are two main patterns of development within animals: direct and indirect. Direct developers are animals such as humans, whose offspring are basically smaller versions of the adult. Indirect developers have a larval stage that can be dramatically different than the adult, and consequently go through a transformation known as metamorphosis. Frogs are a well-known example of vertebrate indirect development, developing first into an aquatic, herbivorous tadpole that later transforms into a terrestrial, carnivorous frog. This transformation is largely regulated by a single hormone—thyroid hormone (TH). Changes in TH play a vital role in tissue transformations such as, differentiation and growth of the limbs, remodeling of the gut tube and liver, as well as resorption of larval features such as the tail. In addition, the timing of metamorphic changes can differ substantially among species. For instance, the average rate of metamorphosis for a majority of frogs/toads (anurans) is between 3-5 weeks, yet there are a multitude of frogs and toads that take several months or even years to go through this process (Duellman and Trueb, 1994; Gilbert, 2010; Petranka, 2007; Provenzano and Boone, 2009). At the other extreme are frogs that have reduced or even eliminated the free-living larval period such as the Eastern Spadefoot toad, Scaphiopus holbrookii, which has one of the shortest larval periods found in metamorphosing frogs or direct developing frogs, like Eleutherodactylus coqui which have no free-living larval stage. This diversity of developmental patterns sparks many questions about the precise molecular and developmental roles TH has on metamorphosis in frogs. How can a single regulator produce such a wide range of responses, not only between species that differ in metamorphic timing, but also among tissues within a single individual? The vast majority of recent studies that examine tissue specific responses to TH have focused on the genes that code for TH binding proteins or for TH receptors (Hollar et al., 2011; Buchholz et al., 2011). However, a very important aspect is being overlooked in these studies, which is the actual level of the TR proteins themselves.
There are three distinct mechanisms that regulate tissue responses to TH: deiodinase enzymes, cytosolic thyroid hormone binding proteins (CTHBPs), and thyroid hormone receptors (TRs) (Morvan-Dubois et al., 2008: Buchholz et al., 2006). The overall objective of the current study is to develop a technique that will allow protein level analysis of two of the three components implicated in the regulation of tissue specific responses to TH during tadpole metamorphosis: CTHBPs and TRs. I hypothesize that changes in the affinity and/or capacity of thyroid hormone receptors and cytosolic thyroid hormone binding proteins to bind TH throughout metamorphosis underlie the timing and extent of tissue remodeling. In fresh tissue, saturation binding assays suggest a difference in binding capacity among tissues.
|Commitee:||Essner, Richard, Williams, Jason|
|School:||Southern Illinois University at Edwardsville|
|School Location:||United States -- Illinois|
|Source:||MAI 53/02M(E), Masters Abstracts International|
|Subjects:||Endocrinology, Developmental biology|
|Keywords:||Amphibian metamorphosis, Thyroid hormone, Thyroid recprtors|
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