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Stem Cells in the Common Fruit Fly Shed Light on Human Genetics

Science, January 9, 2009

Scientists have made a discovery with adult stem cells in the fruit fly, Drosophila melanogaster, which may have important implications for humans.

In a study led by Dr. Michael Buszczak, formerly of the Department of Embryology at the Howard Hughes Medical Institute Research Laboratories in Baltimore, Maryland, and currently in the Department of Molecular Biology at the University of Texas Southwest Medical Center in Dallas, researchers have reported the identification of a protease-encoding gene in Drosophila which is commonly required in germline, epithelial and intestinal stem cells.

Known as the histone H2B ubiquitin protease "scrawny" (scny) gene, the gene encodes a ubiquitin-specific protease and is a common requirement in stem cells within diverse tissue types, since such stem cells share the common need for a chromatin configuration that promotes self-renewal. Chromatin proteins contain the genetic instructions that direct cell function, and are known to regulate multiple types of stem cells.

Among other effects, Dr. Buszczak and his colleagues observed that mutant fruit flies who lacked functional copies of the scrawny gene suffered a premature loss of stem cells in various tissue types which included their skin, intestinal and reproductive tissue.

As the authors conclude in their paper, "Our findings suggest that inhibiting H2B ubiquitylation through 'scny' represents a common mechanism within stem cells that is used to repress the premature expression of key differentiation genes, including Notch target genes."

Although the scrawny gene has only been identified in fruit flies thus far, similar genes are suspected of performing similar functions in other multicellular organisms such as humans. According to Dr. Allan C. Spradling, director of the Carnegie Institution's Department of Embryology, "Our tissues and indeed our very lives depend upon the continuous functioning of stem cells, yet we know little about the genes and molecular pathways that keep stem cells from turning into regular tissue cells - a process known as differentiation. This new understanding of the role played by scrawny may make it easier to expand stem cell populations in culture, and to direct stem cell differentiation in desired directions."

This is not the first time that important clinical therapies for people have been developed from research conducted on the humble fruit fly. Indeed, the unpretentious Drosophila melanogaster has played a central role in the advancement of human medical science for over the past century, ever since the American geneticist and embryologist, Dr. Thomas Hunt Morgan, began studying the common fruit fly in 1906 while at Columbia University. Although a few other scientists prior to Dr. Morgan had conducted experiments with Drosophila, Dr. Morgan became the first person to demonstrate, by studying successive generations of the fruit fly, that genes are transmitted from parents to offspring via chromosomes, which constitute the molecular mechanism of heredity. Such a discovery established the foundation for the entire field of modern genetics, and Dr. Morgan was awarded the 1933 Nobel Prize in Physiology or Medicine, "for his discoveries concerning the role played by the chromosome in heredity." Later, when Dr. Morgan relocated to the California Institute of Technology, he established the Division of Biology at Cal Tech which subsequently produced 7 Nobel Prize winners. To this day, in honor of Dr. Morgan and over half a century after his death in 1945, the Genetics Society of America still awards the annual Thomas Hunt Morgan Medal to one of its members, for outstanding contributions to the field of genetics. As a direct result of Dr. Morgan's discoveries, Drosophila melanogaster continues to serve as a "model organism" of study for genetics and developmental biology, and as such this fruit fly has yielded a number of important discoveries that are applicable to a variety of other species, not only humans. Currently Drosophila is still being studied as a genetic model for many of the most perplexing of human diseases such as diabetes, cancer, and a number of the neurodegenerative diseases including Alzheimer's, Huntington's and Parkinson's diseases, among others.

Like all other species - whether flora or fauna, vertebrate or invertebrate - fruit flies have stem cells too. Unlike many species, however, fruit flies also exhibit a number of traits that lend themselves desirably toward scientific investigation, such as a fast reproductive cycle within a short lifespan, an ease of culturability in large numbers, and a genotype in which mutations are easily inducible and easily trackable by phenotype from one generation to the next. All things considered, fruit flies make a much more compliant and cooperative laboratory specimen to study than humans.



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