Frank A. Laski, Ph.D.

Research

During the past four years we have begun to characterize ovary development using a genetic approach. Our work shows that the ovary will be an excellent system for determining how cells interact with each other during the development of an organ. The Drosophila ovary consists of repeated units, the ovarioles, where oogenesis takes place. The repetitive structure of the ovary develops de novo from a mesenchymal cell mass, a process which is initiated by the formation of a two-dimensional array of cell stacks, called terminal filaments, during the third larval instar. We have studied the development of the terminal filaments and their regular spatial arrangement, as well as the formation of the structurally related basal and interfollicular stalks. We find that they develop through recruitment and cell intercalation of mesenchymal cells, a process resembling the formation of the notochord by convergence and extension in a chordate embryo. Furthermore, we have found that the pattern forming process through which multiple terminal filaments arise from a common cell population requires cell sorting. We believe that a differential distribution of adhesion molecules on the surface of the terminal filament cells is involved in this sorting process. We also find that the Drosophila gene bric · brac (bab) is cell autonomously required for the formation of terminal filaments and is crucial for normal morphogenesis of the ovary. bric · brac has also been shown to be required for proper segmentation and specification in leg primordia, and encodes a nuclear protein which contains a BTB domain, a conserved domain that is found in several transcriptional regulators as well as other proteins. Disruption of terminal filament formation leads to a disruption of ovariole formation and female sterility in bric · brac mutants. We are now in the process of isolating and characterizing new genes that are involved in ovary and limb development.