My long-term goal is to understand the mechanisms that allow cells to breach and traverse through basement membranes. Tightly regulated cell invasions through basement membranes occur frequently in development, enabling cell dispersal and organ formation. Uncontrolled invasive activity also underlies numerous human pathologies, most notably metastatic cancer. The gene regulatory networks that control invasive behavior remain poorly understood, largely because of the lack of in vivo models where this dynamic activity can be rigorously examined. My research is focused on characterizing anchor cell invasion into the vulval epithelium in C. elegans, an in vivo model of cell invasion where powerful single-cell visual and genetic analyses can be combined. The anchor cell is a cell in the developing gonad, which establishes contact with the vulva by extending an invasive process through the basement membrane separating these two tissues that then moves between the central vulval cells. Using classical genetic approaches, we have found that fos-1, the C. elegans ortholog of the proto-oncogene c-fos, plays a specific role in promoting the passage of the anchor cells invasive process through the basement membrane during invasion. C-Fos is overexpressed in numerous metastatic cancers, suggesting that the regulatory networks that control anchor cell invasion are conserved and co-opted by cancer cells. We have also found that netrin signaling plays a critical role in polarizing the actin cystoskeleton within the anchor cell to the site of invasion, where it appears to function in directing cellular protrusions that break through the basement membrane. To further expand our understanding of the genes that regulate anchor cell invasion we have conducted a whole genome RNAi screen that has identified 29 new genes that regulate invasive behavior, most of which are novel candidates for controlling this process. We are coupling this gene identification work with live-cell imaging approaches that utilize GFP-tagged basement membrane components with anchor cell specific expression of the fluorescent protein mCherry to analyze the dynamic interactions of the invading anchor cell and basement membrane. This approach is allowing us to gain a more mechanistic understanding of how the genes that regulate invasion facilitate passage through the basement membrane. One of the most interesting recent findings is that a number of basement membrane components are deposited at the site of invasion, suggesting that modulating the composition of the basement membrane is a necessary requirement to pass through it.