“Maternal Regulators of Oocyte Polarity and Germ Cell Development”

A key research goal of my group is to understand the molecular pathways and cellular events that establish the first developmental axis, the animal-vegetal axis. Since this process is maternally regulated, we use a combination of genetic, molecular, cell biological, and embryological approaches in the zebrafish model system to study oocyte polarity determination. This process was previously not readily tractable in vertebrates in part due a lack of mutants ablating oocyte polarity. Through maternal-effect genetic screens, mutants disrupting oocyte polarity were identified, including bucky ball (buc), the only known gene that is essential for formation of an ancient and conserved polarized structure of primary oocytes, the Balbiani body, and for establishment of early oocyte polarity in a vertebrate. These mutants together with mutants and transgenic models developed in my own lab, and the novel Buc-interacting partners that we have identified through genetic and biochemistry approaches, have provided unprecedented access and a very powerful system to gain mechanistic insight into a fundamental problem of cell and developmental biology- understanding the molecular basis of oocyte polarization and vertebrate animal-vegetal axis formation and germline specification. Our most recent work shows that establishment of oocyte polarity begins with the centrosome in cyst cells and that microtubule organizer activity requires centrosomal localization of Buc to promote oocyte polarity in zebrafish oocytes. We have also identified maternal factors that are necessary for germ cell specification and that promote germ granule formation in the embryo.