S teroid hormones control a wide range of developmental processes in higher organisms, including humans. The biological processes controlled by steroid hormones include the development of secondary sex characteristics, reproductive function, and dietary metabolism. Steroid hormones act in conjunction with receptor proteins to regulate the expression of target genes, ensuring that these genes are activated in the right tissues (tissue-specific gene induction) and at the right times (stage-specific gene induction). These receptors are all part of a related family of proteins called the "nuclear receptor superfamily". Although we have some understanding of how steroid hormones and their receptors control gene transcription in cultured mammalian cells, we understand little about how these effects on gene expression result in the dramatic developmental changes associated with steroid hormone function. The goal of our research is to answer one of the central questions of developmental biology - how can a single hormonal signal elicit different responses at different times and in different tissues during development? This central question is difficult to address using vertebrate animals, because it is difficult to perform whole animal and genetic studies with vertebrates. The fruit fly, Drosophila melanogaster, in contrast, provides an ideal model system for unraveling the molecular mechanisms of steroid hormone action in the context of an intact animal. Drosophila starts life as an embryo, which hatches in to a larva. After several days as a larva, the animal stops crawling, attaches itself to a solid surface, and begins a prepupal stage. The prepupa develops into a pupa in 12 hours, and in another 3-4 days the pupa has developed fully into an adult fly, which emerges from the pupal case. This dramatic transition from larva to adult fly is called metamorphosis.
M etamorphosis is directed by a single steroid hormone called ecdysone. By examining the mechanisms whereby ecdysone regulates metamorphosis in the fly, we hope to gain a better understanding of how steroid hormones control developmental processes in general. In order to determine how ecdysone controls the complex process of metamorphosis, we are studying the genes that are regulated by ecdysone during Drosophila metamorphosis. The betaftz-f1 gene encodes a nuclear receptor superfamily member that appears to play a central role in directing stage-specific genetic and developmental responses triggered by ecdysone. The expression of betaftz-f1is specific to the middle of the prepupal stage. Our work has provided strong evidence in support of the hypothesis that betaftz-f1mediates the ecdysone-response of a set of other regulatory genes, providing them with the competence to be induced by the hormone at the appropriate developmental times. In directing the precise timing of target gene induction by ecdysone, betaftz-f1 ensures that developmental events occur at the correct time, and in the correct temporal order. in order to examine the role of betaftz-f1in development, we are performing a genetic and molecular characterization of the gene. We hope that our studies will provide new insights into the molecular mechanisms of steroid hormone function in Drosophila, and in all animals.
Last Modified 17 July, 2015
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Craig T. Woodard