Roles for UNC-6/Netrin Signaling During Cell Invasion in C. Elegans

Abstract

Basement membranes are dense, sheet-like forms of extracellular matrix thatsurround the epithelial tissues of metazoan organisms. While these structures arecritical for epithelial support and tissue organization, basement membranes also poseformidable barriers to most cells. However, certain specialized cells are able to breachthese barriers and move between tissues. Acquisition of cell invasive behavior by sometumor cells is thought be an important step in cancer progression. Due to the clear basicand clinical importance of understanding the mechanisms underlying cell invasionthrough basement membranes, cell invasive behaviors has been an area of intense study.In this work I examine a developmentally regulated model of cell invasive behavior inthe nematode worm, C. elegans. In this system a single proto-epithelial cell remodelsbasement membrane to connect two epithelial tissues, the uterus and vulva. Using thismodel I identify a novel role for UNC-6/Netrin signaling during this process through basement membranes. I show that Netrin signaling is a third regulatory input for AC invasion that functions partially in parallel to fos-1a and the vulval signal. Further I link netrin signaling to the formation of invasive protrusions that penetrate basement membrane.