Aging is characterized by compromised organ and tissue function. A decrease in stem cell number and/or activity could lead to the aging-related decline in tissue homeostasis. We have analyzed how the process of aging affects germ line stem cell (GSC) behavior in the Drosophila testis and report that significant changes within the stem cell microenvironment, or niche, occur that contribute to a decline in stem cell number over time. Specifically, somatic niche cells in testes from older males display reduced expression of the cell adhesion molecule DE-cadherin and a key self-renewal signal unpaired (upd). Loss of upd correlates with an overall decrease in stem cells residing within the niche. Conversely, forced expression of upd within niche cells maintains GSCs in older males. Therefore, our data indicate that age-related changes within stem cell niches may be a significant contributing factor to reduced tissue homeostasis and regeneration in older individuals.

The conserved Eph receptors and their Ephrin ligands regulate a number of developmental processes, including axon guidance. In contrast to the large vertebrate Eph/Ephrin family, Drosophila has a single Eph receptor and a single Ephrin ligand, both of which are expressed within the developing nervous system. Here, we show that Eph and Ephrin can act as a functional receptor-ligand pair in vivo. Surprisingly, and in contrast to previous results using RNA-interference techniques, embryos completely lacking Eph function show no obvious axon guidance defects. However, Eph/Ephrin signaling is required for proper development of the mushroom body. In wild type, mushroom body neurons bifurcate and extend distinct branches to different target areas. In Eph mutants, these neurons bifurcate normally, but in many cases the dorsal branch fails to project to its appropriate target area. Thus, Eph/Ephrin signaling acts to guide a subset of mushroom body branches to their correct synaptic targets.

At the apical tip of the Drosophila testis, germline and somatic stem cells surround a cluster of somatic cells called the hub. Hub cells produce a self-renewal factor, Unpaired (Upd), that activates the JAK-STAT pathway in adjacent stem cells to regulate stem cell behavior. Therefore, apical hub cells are a critical component of the stem cell niche in the testis. In the course of a screen to identify factors involved in regulating hub maintenance, we identified headcase (hdc). Hub cells depleted for hdc undergo programmed cell death, suggesting that anti-apoptotic pathways play an important role in maintenance of the niche. Using hdc as paradigm, we describe here the first comprehensive analysis on the effects of a progressive niche reduction on the testis stem cell pool. Surprisingly, single hub cells remain capable of supporting numerous stem cells, indicating that although the size and number of niche support cells influence stem cell maintenance, the testis stem cell niche appears to be remarkably robust in the its ability to support stem cells after severe damage.

For more than 30 years the study of learning and memory in Drosophila melanogaster (fruit fly) has used an olfactory learning paradigm and has resulted in the discovery of many genes involved in memory formation. By varying learning programs, the creation of different memory types can be achieved, from short-term memory formation to long-term. Previous studies in the fruit fly used gene mutation methods to identify genes involved in memory formation. Presumably, memory creation involves a combination of genes, pathways and neural circuits. To examine memory formation at the protein level, a quantitative proteomic analysis was performed using olfactory learning and 15N labeled fruit flies. Differences were observed in protein expression and relevant pathways between different learning programs. Our data showed major protein expression changes occurred between short-term memory (STM) and long-lasting memory, and only minor changes were found between long-term memory (LTM) and anesthesia-resistant memory (ARM).

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