Roles for UNC-6/Netrin Signaling During Cell Invasion in C. Elegans
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Basement membranes are dense, sheet-like forms of extracellular matrix that
surround the epithelial tissues of metazoan organisms. While these structures are
critical for epithelial support and tissue organization, basement membranes also pose
formidable barriers to most cells. However, certain specialized cells are able to breach
these barriers and move between tissues. Acquisition of cell invasive behavior by some
tumor cells is thought be an important step in cancer progression. Due to the clear basic
and clinical importance of understanding the mechanisms underlying cell invasion
through 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 in
the nematode worm, C. elegans. In this system a single proto-epithelial cell remodels
basement membrane to connect two epithelial tissues, the uterus and vulva. Using this
model 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.
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Rights for Collection: Duke Dissertations