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Dscam2 mediates axonal tiling in the Drosophila visual system


Sensory processing centres in both the vertebrate and the invertebrate brain are often organized into reiterated columns, thus facilitating an internal topographic representation of the external world. Cells within each column are arranged in a stereotyped fashion and form precise patterns of synaptic connections within discrete layers. These connections are largely confined to a single column, thereby preserving the spatial information from the periphery. Other neurons integrate this information by connecting to multiple columns. Restricting axons to columns is conceptually similar to tiling. Axons and dendrites of neighbouring neurons of the same class use tiling to form complete, yet non-overlapping, receptive fields1,2,3. It is thought that, at the molecular level, cell-surface proteins mediate tiling through contact-dependent repulsive interactions1,2,4,5, but proteins serving this function have not yet been identified. Here we show that the immunoglobulin superfamily member Dscam2 restricts the connections formed by L1 lamina neurons to columns in the Drosophila visual system. Our data support a model in which Dscam2 homophilic interactions mediate repulsion between neurites of L1 cells in neighbouring columns. We propose that Dscam2 is a tiling receptor for L1 neurons.

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Figure 1: Dscam2 is required for visual system development.
Figure 2: Dscam2 restricts L1 arbors to columns.
Figure 3: Dscam2 binds homophilically and its expression is correlated with L1 arbor retraction during development.
Figure 4: Dscam2 homophilic interactions are required for axonal tiling.

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We thank E. DeRobertis, U. Banerjee, W. Grueber, I. Meinertzhagen, A. Sagasti and members of the Zipursky laboratory for comments on the manuscript; J. Clemens for identifying and characterizing the Dscam paralogues; D. Gunning for cloning Dscam3 and Dscam4; G. Marden for providing unpublished reagents that allowed us to generate the Dac-FLP construct; and Y. Zhu and R. Imondi for identifying the two medulla neuron Gal4 lines used in this study. S.L.Z. is an investigator of the Howard Hughes Medical Institute. This work was also supported by the NIH (S.L.Z). S.S.M. was supported by a Cellular Neurobiology training grant from the NIH.

The Dscam2–4 sequences can be found in the NCBI database under accession numbers AE014296, AE003718 and AE003556, respectively.

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Correspondence to S. Lawrence Zipursky.

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Reprints and permissions information is available at The Dscam2–4 sequences can be found in the NCBI database under accession numbers AE014296, AE003718 and AE003556, respectively. The authors declare no competing financial interests.

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Supplementary Figures

This file contains Supplementary Figures S1-S2 with Legends. The Supplementary Figure S1 shows confocal images of Dscam2 mutant phenotypes in three different classes of neurons that project into the medulla (T1 and C3 medulla neurons and lamina neurons). The Supplementary Figure S2 shows confocal images of 10 examples of wild type L1 lamina neurons compared to autonomous and non-autonomous Dscam2 phenotypes generated by MARCM and reverse MARCM. (PDF 2085 kb)

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Millard, S., Flanagan, J., Pappu, K. et al. Dscam2 mediates axonal tiling in the Drosophila visual system. Nature 447, 720–724 (2007).

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