<p>Basement membranes are dense, sheet-like forms of extracellular matrix that</p><p>surround the epithelial tissues of metazoan organisms. While these structures are</p><p>critical for epithelial support and tissue organization, basement membranes also pose</p><p>formidable barriers to most cells. However, certain specialized cells are able to breach</p><p>these barriers and move between tissues. Acquisition of cell invasive behavior by some</p><p>tumor cells is thought be an important step in cancer progression. Due to the clear basic</p><p>and clinical importance of understanding the mechanisms underlying cell invasion</p><p>through basement membranes, cell invasive behaviors has been an area of intense study.</p><p>In this work I examine a developmentally regulated model of cell invasive behavior in</p><p>the nematode worm, C. elegans. In this system a single proto-epithelial cell remodels</p><p>basement membrane to connect two epithelial tissues, the uterus and vulva. Using this</p><p>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.</p> / Dissertation
| Identifer | oai:union.ndltd.org:DUKE/oai:dukespace.lib.duke.edu:10161/5631 |
| Date | January 2011 |
| Creators | Ziel, Joshua W. |
| Contributors | Sherwood, David R |
| Source Sets | Duke University |
| Detected Language | English |
| Type | Dissertation |
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