Search

Brain morphogenesis depends on the maintenance of boundaries between populations of non-intermingling cells. We used molecular markers to characterize a boundary within the optic lobe of the Drosophila brain and found that Slit and the Robo family of receptors, well-known regulators of axon guidance and neuronal migration, inhibit the mixing of adjacent cell populations in the developing optic lobe. Our data suggest that Slit is needed in the lamina to prevent inappropriate invasion of Robo-expressing neurons from the lobula cortex. We show that Slit protein surrounds lamina glia, while the distal cell neurons in the lobula cortex express all three Drosophila Robos. We examine the function of these proteins in the visual system by isolating a novel allele of slit that preferentially disrupts visual system expression of Slit and by creating transgenic RNA interference flies to inhibit the function of each Drosophila Robo in a tissue-specific fashion. We find that loss of Slit or simultaneous knockdown of Robo, Robo2 and Robo3 causes distal cell neurons to invade the lamina, resulting in cell mixing across the lamina/lobula cortex boundary. This boundary disruption appears to lead to alterations in patterns of axon navigation in the visual system. We propose that Slit and Robo-family proteins act to maintain the distinct cellular composition of the lamina and the lobula cortex.

The neuronal wiring of the Drosophila melanogaster visual system is constructed through an intricate series of cell-cell interactions. Recent studies have identified some of the gene regulatory and cytoskeletal signaling pathways responsible for the layer-specific targeting of Drosophila photoreceptor axons. Target selection decisions of the R1-R6 subset of photoreceptor axons have been found to be influenced by the nuclear factors Brakeless and Runt, and target selection decisions of the R7 subset of axons have been found to require the cell-surface proteins Ptp69d, Lar and N-cadherin. A role for the visual system glia in orienting photoreceptor axon outgrowth and target selection has also been uncovered.