Chemotropic cues guide the migrating axons of neurons in the developing nervous system. Netrins are bifunctional guidance cues, attracting or repelling different classes of axons. The attraction to netrins is mediated by DCC whereas repulsion is achieved through Unc5H receptors. In this thesis, we demonstrate that Rho GTPases are required for embryonic spinal commissural axon outgrowth induced by Netrin-1. Using N1E-115 neuroblastoma cells, we have found that Rac1 and Cdc42 activities are required for DCC-induced neurite outgrowth. In fibroblasts, DCC was found to trigger actin reorganization through activation of Rac1. Moreover, we show that Unc5H1 triggers actin reorganization through activation of RhoA in fibroblasts. Using N1E-115 cells we found that Unc5H1 induces neurite outgrowth in a Rac1- and Cdc42-dependent manner. The studies presented in this thesis demonstrate that Rho GTPases are major signaling components of Netrin-1 receptors DCC and Unc5H1.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.98788 |
| Date | January 2005 |
| Creators | Saint-Cyr Proulx, Étienne. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Anatomy and Cell Biology.) |
| Rights | © Étienne Saint-Cyr Proulx, 2005 |
| Relation | alephsysno: 002332370, proquestno: AAIMR24789, Theses scanned by UMI/ProQuest. |
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