Genetic screens provide information on phenotype interactions as a step to uncovering functional interactions in vivo. In this study, I conducted genetic modifier screens in Drosophila that might reveal genes expressed in the embryonic CNS that interact genetically with slit. These screens include a blind genetic screen, stable line double mutant analysis, transheterozygote interactions and a dosage-sensitive dominant modifier screen. Differences in CNS phenotypes between the blind screen and the double mutant analysis were uncovered for some of the crosses, indicating background effects of genotype can influence phenotypes observed. A group of candidate genes were chosen based on motif composition for potential
interaction with slit, and spatial and temporal expression patterns coinciding with Slit. The
majority of these genes show a mutant CNS phenotype on their own. slit-interacting genes
were identified by their ability to alter midline axon guidance, as assayed with antibodies
specific to CNS-expressing proteins. The interacting genes include those encoding receptor and second messengers thought to function in growth cones, integrins and extracellular matrix proteins. From these interactions, I could then propose models of function in axon guidance. The first model I propose adds to a currently known repressor-derepressor model
of axon guidance at the midline of the CNS, involving the Netrin, Commissureless and
Robo signaling molecules, whereby Slit is locally suppressed by Netrin function to allow
axons to cross the midline via Comrnissureless-mediated intemalisation of Robo. In my
second model, Slit may also be involved in integrin signaling, especially through the αPS3
and βPS integrins, in concert with the Laminin molecule. Included in this model is the
intersection of cytoplasmic Dock signaling within the growth cone. Thirdly, I demonstrate
a genetic interaction with other molecules expressed by the midline glia, Masquerade, Toll
and Neurexin. Masquerade and Toll may function in a common pathway, but in parallel to
Slit function. Likewise, Neurexin may function in a parallel pathway to Slit. Slit has shown to interact genetically with a number of molecules that appear to be involved in different aspects of axon guidance. This study was meant to provide a survey of molecules that may functionally interact with Slit and provides a good basis upon which to explore the interactions in detail in future work. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22465 |
| Date | 07 1900 |
| Creators | Stevens, Adrienne |
| Contributors | Jacobs, J. Roger, Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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