A Genetic Screen to Identify Novel Genes Involved in Stem Cell Maintenance

Adult stem cells are responsible for producing the body’s differentiated cells including blood, skin, intestinal epithelia, and sperm. Regulation of these cells is essential in that organisms must be able to provide an adequate supply of differentiated cells as well as to maintain existing stem cell populations. Failure to properly regulate populations of adult stem cells can have serious consequences—loss of stem cells can lead to tissue degeneration whereas overproliferation may eventually lead to cancer.

In the male germline of Drosophila, two different populations of stem cells reside in a stem cell niche—a microenvironment responsible for regulating self-renewal. Traditionally, research has emphasized communication between the niche and the stem cell populations. However, recent research suggests that communication between the two stem cell populations is equally important. Therefore, it is possible that novel genes regulating signaling between the two stem cell populations may exist.

Using a forward genetic screen, we plan to identify novel factors that regulate stem cell maintenance. To accomplish this, we induced mutagenesis and then screened using a Flipase/FRT screen to identify interesting phenotypes, which were then mapped to the causative genes.  We have identified one overproliferation mutation in Star, which regulates Spitz, an EGF pathway ligand. Additionally, we have identified a stem cell loss mutation in AIF which codes for a protein involved in both apoptosis and mitochondrial function. With this work, we plan to identify more genes involved in stem cell maintenance and determine potential roles in signaling among different stem cell populations.