The Story
Flies, Eggs and Sperm
What does make a sperm a sperm and an egg an egg? In the context of Drosophila Melanogaster fruit flies, Professor of Biology Matthew Wawersik spends his time exploring that question by studying the behavior of germ cells in fly embryos.
A graduate of Colorado State University who received his Ph. D. from the Johns Hopkins School of medicine, Wawersik came to William and Mary in 2005 and began his research on Drosophila, inspired by the studies of the lab in which he worked as a postdoctoral fellow prior to coming to The College. During this time, he participated in studies of the relationship between germ cells and somatic gonad cells in adult animals. Now, he investigates this relationship in the embryonic stage, where it all begins.
In all sexually reproducing animals, sperm and eggs are produced in organs universally termed gonads. In any gonad, there are two types of cells: germ cells which divide to produce the actual sperm and egg cells, and “somatic cells” which provide support and chemical instructions for the germ cells. In the embryo, the two do not initially develop together; rather, the somatic gonadal precursor cells (SGPs) and primordial germ cells (PGCs) originate at opposite ends of the young embryo and “migrate” to a rendezvous.
In Drosophila, this meeting occurs a mere 24 hours after fertilization. At this point, chemical signals from the SGPs instruct the PGCs to follow either a male or female path of development and go on to produce sperm or eggs. These chemical signals bind to receptors on the PGC membrane and activate specific proteins called transcription factors, which go on to regulate gene expression: which genes are turned “on” and “off.”
Wawersik and his lab have recently made the discovery that one particular set of these chemical interactions called the JAK/STAT pathway is significantly responsible for the development of male PGCs into sperm-producing cells.
In a study published in 2005, Wawersik examined the behavior of genetically female PGCs in female embryos where the surrounding somatic tissue (SGPs) had been artificially masculinized by genetic mutations. The specific embryos in this study had mutations that allowed the expression of the JAK/STAT pathway in an otherwise wholly female environment. Amazingly, the PGCs in the interaction started dividing in a manner consistent with spermatogenesis.
By giving the surrounding cells a “sex change,” as Wawersik calls it jokingly, he was able to induce genetically female germ cells to behave as if they were male.
In adult flies, abnormalities in the embryonic generation of gonads are typically manifested as infertility and germ cell tumors. As Wawersik puts it: “Germ cells being confused, and not being regulated properly by their external environment.” And many of these biochemical mechanisms are conserved along the evolutionary scale.
In mice, a similar pathway involving retinoic acid is related to germ cell sex determination. And in humans, certain cancers of the germ cells linked to errors in SGP signaling of PGCs exist, such as the extreme and bizarre teratoma in which uncontrolled cell differentiation of embryonic GSCs produces a wide range of body tissues in a single tumor"occasionally including hair and fully formed teeth.
Sadly, a fast-growing fetal teratoma can result in stillbirth; most are no diagnosed until later life. Errors in germ cell sex determination may also result in sterility in adults; Wawersik and others have demonstrated this effect has been demonstrated in flies.
The application of his findings to the treatment of human disorders is one of the directions Wawersik would like to see his field of research take; Wawersik himself plans to continue elucidating the mechanism of the JAK/STAT pathway in germ cell sex determination and continue his search for other similar pathways.
According to Wawersik’s studies, however, not all germ cell characteristics are governed by interactions with gonadal somatic cells (SGPs). In 2005, he identified one particular chemical present in the cytoplasm of all primordial germ cells (PGCs), termed nanos, which is required for the formation of an organelle (cell structure) called a spectrosome.
Spectrosomes are found in both male and female germ cells and are essential to their functioning. Wawersik found that these structures are formed in PGCs regardless of whether or not they have rendezvoused with the SGPs in the fly embryo, and regardless of any chemical signals sent by the SGPs. While the alignment of PGC germ cells with one particular sexual identity is fairly fluid, the identity of PGCs as PGCs is not, at least with regards to spectrosome formation.
Currently, Wawersik is researching the function of the aforementioned JAK-STAT pathway, known to confer maleness in conjunction with SGPs, in determining PGCs as PGCs; perhaps in addition to promoting maleness, the JAK-STAT pathway promotes “PGC-ness” at some stage of early PGC development, and is later manually switched off in normal females. In time, the flies will tell.