| Abstract No.: | C-A3004 |
| Country: | Canada |
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| Title: | NEURON-GLIAL INTERACTIONS THROUGH DL-N SIGNALLING PROMOTES GLIAL CELL SUBTYPE DIVERSITY |
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| Authors/Affiliations: | 1 Stephanie Stacey*;
1 McGill University, Montreal, QC, Canada
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| Content: | Objectives: Reciprocal interactions between neurons and glial cells are vital for the development and maintenance of neural circuits. An important challenge is to understand the extent of the functional diversity among glial cells, and to discover how functionally diverse glial cell subtypes arise during development. Utilizing the advanced genetic model system of Drosophila melanogaster, our lab has shown previously that signalling through the Notch (N) receptor is important for subtype specific gene expression in glial cells. Our lab found that a key regulator of this signalling event was the glycosyltransferase Fringe (Fng), which renders glia sensitive to N activation by Delta (Dl), an N ligand provided by neurons. My research will concentrate on the importance of Dl-N signalling through neuron-glial interactions for glial cell differentiation. I will focus on a subset of glial cells in the Drosophila CNS called the longitudinal glia (LG). LG lie close to CNS axon projections, dendrites and synapses. Due to their positioning and distinctive molecular properties, the LG provide an excellent model with which to study glial subtype differentiation and neuron-glial interactions.
We propose that N signalling promotes the specification of functionally distinct glial cell subtypes, reflected by expression of subtype-specific genes. Our objectives are to 1) Identify genes whose expression in LG is regulated by neuron-glial communication through Dl-N signalling 2) Investigate how the LG may modulate CNS function.
Materials and Methods: I used the embryonic CNS of Drosophila to characterize neuron-glial interactions. I applied both immunhistochemical and in situ hybridization techniques to analyze gene expression in this model system.
Results: I performed a screen of 29 LG-specific genes and found that the expression of six of these genes was influenced by N signalling: two were positively regulated by N and four were inhibited. To extend these observations, I tested whether these N responsive genes were dependent on Fng and on axon-derived Dl. I examined their expression in fng mutants and found that the expression of all six N-sensitive genes was altered. I then tested whether these genes responded to neuronal Dl by manipulating Dl function in neurons which contact LG. In this case, I found that expression of only one N-sensitive gene was changed. I performed locomotion assays with various genotypes of larvae where N signalling was impaired in the LG to begin to investigate a possible role for the LG in CNS function. These experiments will determine how neuron-glial communication through the N pathway regulates glial gene expression, and possibly function, in vivo.
Conclusions: Drosophila LG provide an advanced and accessible model to study neuron-glial relationships in the CNS and may provide insights into the development and maintenance of the mammalian CNS. Together, these experiments will significantly advance our understanding of the regulation and consequences of N signalling through neuron-glial interactions.
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