Analysis of target-derived factors regulating axon guidance in the visual system of Drosophila.

Bazigou, Eleni (2006). Analysis of target-derived factors regulating axon guidance in the visual system of Drosophila. PhD thesis The Open University.



The developing visual system of Drosophila is characterized by complex and stereotyped patterns of neuronal connections. The Drosophila compound eye consists of approximately 800 ommatidia, each containing 8 photoreceptor cells (R-cells, R1-R8). Each of these R-cell groups have distinct spectral sensitivity and target specificity. Rl-R6 axons terminate in the first optic ganglion called the lamina, inbetween two rows of glial cells, the epithelial and marginal glia, whereas R7 and R8 axons project through the lamina and terminate in the second optic ganglion, the medulla.

Previous studies have demonstrated that epithelial and marginal glia regulate target layer selection of R1-R6 in the lamina. To systematically address the molecular mechanisms through which glial cells as well as target neurons guide R-cell axons to establish initial projection pattern, the lab devised an FLP/FRT system-based genetic approach (ELF system) to generate somatic clones specifically in target cells. Using ELF in a large-scale mutagenesis screen for the left arm of the second chromosome, we isolated mutant candidates with R-cell projection defects caused by genes required in the target.

In a candidate approach, the role of the Drosophila homolog of the receptor tyrosine kinase Anaplastic lymphoma kinase (Aik) and its activating ligand Jelly belly (Jeb), known for their role in the development of the Drosophila visceral mesoderm, was addressed in our system. Aik and Jeb show a highly dynamic and initially complementary expression pattern in the target and in R-cells, respectively. Loss of Aik from the target and jeb from the eye has revealed common target specificity defects of R1-R6 axons in the lamina and R8 axons in the medulla during the refinement of axonal projections in the optic lobe. This novel anterograde signaling system in the Drosophila visual system may be regulating R1-R6 and R8 target specificity by controling the modulation of one or more axon guidance cues present in the target.

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