Allan Spradling

Structure and Function of Female Germ Cells

Each generation, germ line cells carry out two major functions. First, they propagate their own intricate, information-rich contents in an essentially undamaged state, thereby continuing an unbroken chain of inheritance from their germ cell ancestors stretching back billions of years. Secondly, female germ cells choreograph early embryonic development, which establishes essential conditions for germ line-derived somatic cells to produce a new, but transient organism. The Spradling lab studies several of the processes germ cells use to accomplish these fundamental tasks by conducting molecular genetic studies of the fruit fly Drosophila and of mice.

How can germ line cells proliferate, seemingly without limit, while somatic cells age and die? One group of cellular organelles, the mitochondria, produce energy by oxidative processes that generate highly reactive and potentially damaging by-products. Despite this, mitochondria contain their own small genome, encoded by mitochondrial DNA. Damage to mitochondrial DNA has recently been shown to cause several human diseases, and to occur spontaneously in aging somatic cells. Spradling's group has begun to analyze how new mitochondria are produced during the process of egg formation and to learn how germ cells are able to furnish succeeding generations of somatic cells with functional, undamaged mitochondrial genomes.

Spradling believes that keys to understanding this and several other aspects of germ cell biology can be found during a little-studied, early stage of germ cell development, when small groups of germ cells transiently become interconnected with one another into cell clusters. During this time, membrane-rich cellular constituents, including mitochondria, aggregate within an unusual structure -- the fusome -- that extends throughout all the cells in the cluster. The scientists are identifying the genes and mechanisms used to program cell cluster and fusome formation, and are gaining insight into the function of these processes.

Even earlier in their generational cycle, Drosophila germ cells proliferate extensively as stem cells. Germ line stem cells represent one of the best systems currently available to study the molecular mechanisms that control stem cell proliferation -- a fundamental process underlying the maintenance of many adult tissues. The lab's work has implicated the regulated translation of stored messenger RNAs as a critical process used by stem cells and has identified a likely key target of such regulation. Moreover, the researchers discovered extracellular signals from nearby somatic cells that are needed to maintain the stem cell's fate. They are also studying mechanisms that germ line cells use to silence the expression of unwanted genes, such as those of invading viruses and transposable elements.

Finally, Spradling and his lab members recognize that progress in biology often comes from improved methods. They continue to participate in the Drosophila genome project. Their current goal is to further facilitate studies of gene function by isolating insertional mutations in greater than 85% of all genes identifiable in the genome sequence.