Fly Research Gives Insight to Human Stem Cell and Cancer
For a fertilized egg to give rise to an organism made up of billions or trillions of cells, a precise program of cell divisions must unfold
Stem cells are a recurring topic among the presentations given at the Genetics Society of America's 53rd Annual Drosophila Research Conference, March 7-11, 2012, at the Sheraton Chicago Hotel & Towers.
Specifically, researchers are trying to determine how cells specialize within organs, while stem cells maintain tissues and enable those tissues to repair damage and respond to stress and aging.
Some cell divisions are "asymmetric": one of the two daughter cells specializes, yet the other retains the ability to continue dividing. Chris Q. Doe, Ph.D., professor of biology at the University of Oregon, compares this asymmetric cell division to splitting a sundae so only one half gets the cherry. The "cherry" in a cell are the proteins and RNA molecules that make one cell different from the other. The collection of different molecules in different regions of a cell before it divides determines "cell polarity."
Dr. Doe and his team trace cell divisions that form a fly's nervous system. "Producing the right cells at the right time is essential for normal development, yet it's not well understood how an embryonic precursor cell or stem cell generates a characteristic sequence of different cell types," he says.
Dr. Doe and his team traced the cell lineages of 30 neuroblasts (neural precursor cells that become stem cells). With each cell division a daughter cell becomes destined for specialization, and a second daughter cell becomes a self-renewing neuroblast. Development is a matter of balance. Self-renew too much, and a tumor results; not enough, and the brain shrinks.
Tracing a cell lineage is a little like sketching a family tree of cousins who share a great-grandparent except that the great-grandparent (the neuroblast) continually produces more cousins. Not only are there ever more cells but, "The offspring will change due to the different environments they are born into," says Dr. Doe.
Julie A. Brill, Ph.D., a principal investigator at The Hospital for Sick Children (SickKids) in Toronto, investigates cell polarity in sperm cells. These highly specialized elongated cells begin as round precursor cells. Groups of developing sperm elongate, align and then condense their DNA into tight packages, develop enzyme-containing bumps on their tips (that will burrow through an egg's outer layers), form moving tails, and finally detach and swim away.
The Brill lab studies a membrane lipid called PIP2 (phosphatidylinositol 4,5-bisphosphate) that establishes polarity in developing male germ cells in Drosophila.
"Reducing levels of PIP2 leads to defects in cell polarity and failure to form mature, motile sperm," Dr. Brill says. These experiments show that localization of the enzyme responsible for PIP2 production in the growing end of elongating sperm tails likely sets up cell polarity. Since loss of this polarity is implicated in the origin and spread of cancer, defects in the regulation of PIP2 distribution may contribute to human cancer progression, she adds.
Stephen DiNardo, Ph.D., the Institute for Regenerative Medicine at the University of Pennsylvania, investigates how different types of stem cells in the developing fly testis give rise to germ cells and epithelial cells that encircle the germ cells, as well as daughter cells able to self-renew. For each of these roles, stem cells are guided by their niche environment.
Dr. DiNardo explains: "We study how these niche cells are first specified during development, how they assemble, and what signals they use. Elements of what we and others learn about this niche may well apply to more complex niches in our tissues."
Denise J. Montell, Ph.D., Johns Hopkins University, works on the female counterpart to the testis, the fly ovary. She and her co-workers use live imaging and fluorescent biomarkers to observe how the contractile proteins actin and myosin assemble, disassemble, and interact, elongating tissues to construct the egg chamber.
Each approach adds value to observing the developing ovary undergo environmental changes. "Starvation, for example, slows the rate of stem cell division and induces some egg chambers to undergo apoptosis (die) while others arrest until conditions improve," she says.
Dr. Montel's group has made the surprisingly observation that following starvation and re-feeding, some of the cells that got far along the cell death pathway actually reversed that process and survived.
Montel's group has documented this "reversal of apoptosis" in a variety of mammalian cell types including primary heart cells. The observation has many intriguing implications as it may represent a previously unrecognized mechanism that saves cells difficult to replace, which may have implications for treating degenerative diseases.
THE GSA DROSOPHILARESEARCH CONFERENCE: At least 1,500 researchers attend the annual GSA Drosophila Research Conference to share the latest research using the fruit fly Drosophila melanogaster and other insect species. Many of findings from these model organisms have broad application for the study of human genetic traits and diseases. For more information about the conference, seewww.drosophila-conf.org/2012/.
ABOUT GSA: Founded in 1931, the Genetics Society of America (GSA) is the professional membership organization for scientific researchers, educators, bioengineers, bioinformaticians and others interested in the field of genetics. Its nearly 5,000 members work to advance knowledge in the basic mechanisms of inheritance, from the molecular to the population level. The GSA is dedicated to promoting research in genetics and to facilitating communication among geneticists worldwide through its conferences, including the biennial conference on Model Organisms to Human Biology, an interdisciplinary meeting on current and cutting edge topics in genetics research, as well as annual and biennial meetings that focus on the genetics of particular organisms, including C. elegans, Drosophila, fungi, mice, yeast, and zebrafish. GSA publishes GENETICS, a leading journal in the field and a new online, open-access publication, G3: Genes|Genomes|Genetics. For more information about GSA, please visitwww.genetics-gsa.org. Also follow GSA on Facebook atfacebook.com/GeneticsGSA and on Twitter @GeneticsGSA.