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The protocadherin Flamingo is required for axon target selection in the Drosophila visual system

Abstract

Photoreceptor neurons (R cells) in the Drosophila visual system elaborate a precise map of visual space in the brain. The eye contains some 750 identical modules called ommatidia, each containing eight photoreceptor cells (R1–R8). Cells R1–R6 synapse in the lamina; R7 and R8 extend through the lamina and terminate in the underlying medulla. In a screen for visual behavior mutants, we identified alleles of flamingo (fmi) that disrupt the precise maps elaborated by these neurons. These mutant R1–R6 neurons select spatially inappropriate targets in the lamina. During target selection, Flamingo protein is dynamically expressed in R1–R6 growth cones. Loss of fmi function in R cells also disrupts the local pattern of synaptic terminals in the medulla, and Flamingo is transiently expressed in R8 axons as they enter the target region. We propose that Flamingo-mediated interactions between R-cell growth cones within the target field regulate target selection.

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Figure 1: Mosaic fmi animals show defective optomotor response but normal R1–R6 target layer specificity.
Figure 2: The flamingo gene is required for R1–R6 axons to choose the appropriate pattern of targets in the developing lamina and is expressed in R1–R6 growth cones.
Figure 3: Functional flamingo is required for assembly of synaptic units, called cartridges, in the lamina.
Figure 4: Synapses in laminas innervated by mutant photoreceptors do not differ from those in control laminas.
Figure 5: Functional flamingo is required in R8 for elaboration of precise array in the medulla.
Figure 6: flamingo is required in R8 to form a smooth topographic map along the dorsoventral axis.
Figure 7: R-cell axons form a topographic map.
Figure 8: Flamingo protein is transiently expressed in R8 axons as they enter the optic lobe.

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Acknowledgements

We thank the members of the Zipursky lab and U. Banerjee for comments on the manuscript, and T. Uemura for the anti-Flamingo antibodies. We also thank B. Dickson and T. Uemura for sharing results prior to publication. We thank K. Ronan for assistance in preparing the manuscript, R. Kostyleva for help with EM and J. A. Horne for EM computer methods. This work was supported by postdoctoral fellowships from the Jane Coffin Childs Foundation (T.R.C.), the Burroughs-Wellcome Fund for Biomedical Research (T.R.C.), the Life Science Research Foundation (HHMI) (C.-H.L.), an NIH Medical Scientist Training Program grant (GM08042 to R.L.) and a grant from the National Eye Institute (EY03592 to I.A.M.). I.A.M. is a Guggenheim Fellow; S.L.Z. is an Investigator of the Howard Hughes Medical Institute.

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Correspondence to S Lawrence Zipursky.

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Supplementary information

Supplementary Fig. 1.

The sorting of R1-R6 axons in wild type (upper panel) and in flamingo (lower panel) is shown schematically. In wild type, each ommatidium sends a single fascicle of axons into the brain. These axons are arranged in a precise fashion with R8 in the middle surrounded by the remaining 7 (inset with R8 gray, R7 white and R1-R6 black). The R7 and R8 axons extend through the lamina (shown as an array of large open circles) and into the medulla. At the distal surface of the lamina, the R1-R6 growth cones extend laterally to specific targets that are arranged in a stereotyped pattern. Flamingo mutant R cells from a single ommatidium form axon fascicles that are arranged in a fashion similar to wild type. As in wild type, the R7 and R8 axons project through the lamina and the R1-R6 axons terminate in the lamina. R1-R6 growth cone sorting at the surface of the lamina is abnormal. As a consequence, R1-R6 axons innervate an inappropriate pattern of targets. Some lamina units, or cartridges, are hyperinnervated (arrow) while others are hypoinnervated (light gray arrowhead) as compared to wild type (dark gray arrowheads in the upper panel). (JPG 57 kb)

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Lee, R., Clandinin, T., Lee, CH. et al. The protocadherin Flamingo is required for axon target selection in the Drosophila visual system. Nat Neurosci 6, 557–563 (2003). https://doi.org/10.1038/nn1063

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