Establishment of precise neuronal connections requires the proper guidance and targeting of growing axons during embryogenesis. The growth cone, a sensori motor structure at the leading edge of the axon, expresses cell surface receptors for recognizing guidance and targeting signals. It also possesses the intracellular signal transduction machinery to convert the extracellular signals into the reorganization of cytoskeletal structures in inducing directed movement (guidance) or the cessation of movement (targeting). Accumulated evidence points to the importance of protein tyrosine phosphorylation in growth cone signaling. The signaling cascade linking tyrosine phosphorylation into the changes in growth cone motility, however, remains largely undefined. Previous studies suggest that the Dock/Nck adapter protein play a role in transducing tyrosine phosphorylation signals to the actin-based cytoskeleton to regulate growth cone motility. To gain insight into the Dock signaling pathway, we have sought to identify the downstream effector of Dock in photoreceptor (R-cell) growth cones in the Drosophila visual system. Our recent results indicate that Misshapen (Msn), a Ste20-like Ser/Thr kinase, functions downstream of Dock to terminate R-cell growth cones in the target region. First, like loss of dock, mutations in msn cause R-cell growth cone targeting defects. Second, Msn is expressed in R-cells and predominantly localized in R-cell growth cones. Third, overexpression of Msn induces the early growth cone termination, a phenotype that is opposite to the msn loss-of-function phenotype. Finally, Msn interacts with Dock physically and genetically. We propose that Dock-linked target-derived signals activate Msn, which in turn modulates cytoskeletal-related proteins within the growth cones in decelerating their motility when the axons reach their targets. To identify genes that genetically interact with Msn, I screened ∼150 deficiency lines. I identified 29 cytological
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.33445 |
| Date | January 2000 |
| Creators | Ruan, Wenjing, 1967- |
| Contributors | Rao, Yong (advisor) |
| 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 Neurology and Neurosurgery.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001770381, proquestno: MQ70751, Theses scanned by UMI/ProQuest. |
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