In Caenorhabditis elegans, body muscles extend muscle arms in a chemotropic
fashion to the nearest nerve cord and serves as a model for the investigation of guided
cell migration. I found that the transmembrane receptor UNC-40/DCC is required, and
functions cell-autonomously to regulate muscle arm extension. Surprisingly, both the
canonical ligand of UNC-40 (UNC-6/Netrin) and the extracellular domains of UNC-40
are dispensable, suggesting that UNC-40 relies on a co-receptor or other polarizing
pathways to direct muscle arm extension. Furthermore, through double mutant analyses
and the use of a neomorphic phenotype induced by UNC-40 over-expression, I define a
distinct UNC-40 pathway in which UNC-73/Trio, the WAVE actin polymerization
complex, and components of the dense body likely act downstream of UNC-40 to
regulate muscle arm extension. Distinct modes of UNC-40’s function in muscle arm
extension compared to its role in neurons provide a more complete understanding of how
this conserved guidance receptor functions.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/29979 |
| Date | 16 September 2011 |
| Creators | Chan, Kevin Ka Ming |
| Contributors | Roy, Peter John |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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