Drosophila melanogaster is one of leading model organisms in which genetic manipulation can be applied to help elucidate the fundamental mechanisms of metazoan biology.

One such process is the biology of stem cells.  Special microenvironments known as “niches” maintain adult tissue stem cells and stimulate them to divide.  By identifying and studying several types of Drosophila stem cells and niches, often for the first time, we are uncovering general principles and genetic pathways controlling stem cell regulation.  Stromal niches, such as those that sustain germline stem cells (GSCs) and their partner escort stem cells (ESCs) in the ovary, require specific tissue cells, including non-dividing cap cells.  Two other niches are found nearby that each house a single somatic stem cell (SSC), the precursor of the follicle cells that surround developing follicles.  A fourth type of adult stem cell, midgut intestinal stem cells (ISCs), do not associate with a specific stromal cell, but do lie adjacent to the basement membrane that separates endoderm from gut circular muscle.  We are studying the cellular behavior and molecular regulation of all these stem cells and their niches.  Cell replacement, reversion, and directed migration all contribute to stem cell homeostasis.  Moreover, we are starting to define specific genes involved in the chromatin organization of stem cells and their immediate daughters.

A second area of focus is ovarian biology.  We have analyzed several aspects of egg development that are intrinsically important, but that also address whether  molecular processes of oogenesis are conserved across species as diverse as flies and mice.  These include germline cyst formation, the role of the fusome, mitochondrial inheritance via the Balbiani body, and the control of oogenesis by steroid hormones and prostaglandins.

Finally, we continue to help develop new technology for Drosophila genetic research.  We remain part of the Drosophila gene disruption project, a multi-group effort to identify strains bearing single marked transposon insertions in every Drosophila gene.  We recently completed a multi-year project to develop the “Carnegie Collection” of protein trap strains, each of which fuse a different Drosophila gene or transcript to green fluorescent protein (GFP).  Analyzing the patterns of gene expression revealed by these strains, including the subcellular locations of the fusion proteins, provides a powerful complement to standard genetics in identifying gene products that contribute to stem cell and to ovarian biology.