Year of Publication


Degree Name

Doctor of Philosophy (PhD)

Document Type



Arts and Sciences



First Advisor

Dr. S. Randal Voss


For nearly a century, amphibian metamorphosis has served as an important model of how thyroid hormones regulate vertebrate development. Consequently metamorphosis has been studied in a number of ways including: morphologically, developmentally, ecologically, and from an endocrine perspective. Over the last two decades, much has been learned about the molecular basis of anuran (frog) metamorphosis. However, very little is known about the molecular underpinnings of urodele (salamander) metamorphosis. Using the axolotl and axolotl hybrids as models, I present some of the first studies on the gene expression changes that occur during urodele metamorphosis. In Chapter 1, the motivation for the research described in the subsequent chapters is presented and the literature is briefly reviewed. In Chapter 2, the first microarray analysis of urodele metamorphosis is presented. This analysis shows that hundreds of genes are differentially expressed during thyroid hormone-induced metamorphic skin remodeling. Chapter 3 extends the analysis presented in Chapter 2 by showing that the transcriptional patterns associated with metamorphic skin remodeling are robust even when the concentration of thyroid hormone used to induce metamorphosis is varied by an order of magnitude. Chapter 4 makes use of the differentially expressed genes identified in Chapters 2 and 3 to articulate the first model of urodele metamorphosis to integrate changes in morphology, gene expression, and histology. In addition, Chapter 4 outlines a novel application for piecewise linear regression. In turn, Chapter 5 makes use of the model presented in Chapter 4 to demonstrate that full siblings segregating profound variation in metamorphic timing begin to diverge in phenotype early during larval development. In Chapter 6 the conclusions drawn from the research are summarized and future directions are suggested.

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