Brown Lab

RESEARCH INTERESTS

Amphibian Metamorphosis

Metamorphosis in frogs and toads is a set of complex developmental programs controlled by thyroid hormone (TH). The pervasive and dramatic changes that occur as a tadpole turns into a frog have captured the attention of life scientists from many disciplines. For evolutionary biologists, the extent to which related organisms incorporate metamorphosis in their life cycle is of paramount interest. For specialists who study cell death, a burgeoning field of research interest, apoptosis is a major event in metamorphosis. TH can induce it in many tissues, even in whole organs. For endocrinologists, TH-induced metamorphosis is a model for the general problem of the molecular basis of TH action and the interaction of the hypothalamus, the pituitary, and the thyroid glands. However, the emphasis in our laboratory is the use of amphibian metamorphosis to study complex developmental programs such as vertebrate organogenesis, which can be initiated by the simple addition of TH to the tadpole's rearing water. 

A developmental program is affected through the expression of many genes, causing changes in phenotype. The traditional way to study complex programs has been to identify mutants that change the phenotype. However, there are many important programs that one would like to study in organisms that are not suitable for traditional genetics. This list includes vertebrate organogenesis, amphibian metamorphosis, tissue and organ regeneration, changes afterbirth in mammals, diseased versus normal tissues, the action of hormones or drugs on their target tissues or organs, and the influence of various environmental stimuli on a particular organ. 

The later that a program is expressed in the life cycle of any organism, including those suited for genetics, the more difficult it will be to use traditional genetics. An alternative approach to the analysis of complex programs utilizes molecular biological methods that isolates and identifies genes whose expression change as the programs are executed.

We have developed a strategy that is generally applicable to the analysis of complex programs, using TH induced metamorphosis in Xenopus laevis as a model. We have identified genes that are regulated by TH in a variety of tissues and organs by hybridizing probes with micro arrays prepared by Agilent Technologies. The results can be accessed at Micro array analysis to study Xenopus laevis metamorphosis.  Our first array publication is Das et al. Dev. Biol. (2006).