The AC/VU decision provides a simple model system to study lateral specification during development (reviewed in 1). Two cells of the somatic gonad, Z1.ppp and Z4.aaa, have equivalent developmental potential in that either one may become the anchor cell (AC) or a ventral uterine precursor cell (VU). LAG-2, a ligand of the DSL family, and LIN-12, a receptor of the LIN-12/Notch family, mediate interactions between Z1.ppp and Z4.aaa, so that only one AC is formed. Genetic mosaic analysis has shown that the cell with higher
lin-12 activity will always take on the VU fate, and suggested that a feedback mechanism amplifies a difference in
lin-12 activity (2). Expression studies have further shown that feedback occurs at the level of transcription during the AC/VU decision. Specifically, before the decision, both Z1.ppp and Z4.aaa express
lin-12 and
lag-2 . As the decision progresses
lin-12 transcription becomes restricted to the presumptive VU whereas
lag-2 transcription becomes restricted to the presumptive AC (3). The expression studies suggest the existence of two types of feedback loop within the receiving cell: the downregulation of
lag-2 transcription and the upregulation of
lin-12 transcription, both occurring only upon
lin-12 activation. We are interested in identifying other components of these feedback loops. We are beginning by examining candidate genes based on homology to genes in Drosophila , where a negative feedback loop that represses Delta expression upon Notch activation has been described (1). In the future, we hope to undertake genetic screens for new genes that are involved in feedback loops during the AC/VU decision. 1. I. Greenwald, Genes & Development 12, 1751-1762 (1998). 2. G. Seydoux, and I. Greenwald, Cell 57, 1237-1245 (1989). 3. H. A. Wilkinson, K. Fitzgerald, and I. Greenwald, Cell 79, 1187-1198 (1994).