Letter | Published:

Coordinate control of synaptic-layer specificity and rhodopsins in photoreceptor neurons

Nature volume 456, pages 795799 (11 December 2008) | Download Citation


This article has been updated


How neurons make specific synaptic connections is a central question in neurobiology. The targeting of the Drosophila R7 and R8 photoreceptor axons to different synaptic layers in the brain provides a model with which to explore the genetic programs regulating target specificity. In principle this can be accomplished by cell-type-specific molecules mediating the recognition between synaptic partners1. Alternatively, specificity could also be achieved through cell-type-specific repression of particular targeting molecules. Here we show that a key step in the targeting of the R7 neuron is the active repression of the R8 targeting program. Repression is dependent on NF-YC, a subunit of the NF-Y (nuclear factor Y) transcription factor2. In the absence of NF-YC, R7 axons terminate in the same layer as R8 axons. Genetic experiments indicate that this is due solely to the derepression of the R8-specific transcription factor Senseless3 (Sens) late in R7 differentiation. Sens is sufficient to control R8 targeting specificity and we demonstrate that Sens directly binds to an evolutionarily conserved DNA sequence upstream of the start of transcription of an R8-specific cell-surface protein, Capricious (Caps) that regulates R8 target specificity. We show that R7 targeting requires the R7-specific transcription factor Prospero4,5 (Pros) in parallel to repression of the R8 targeting pathway by NF-YC. Previous studies demonstrated that Sens6,7 and Pros8 directly regulate the expression of specific rhodopsins in R8 and R7. We propose that the use of the same transcription factors to promote the cell-type-specific expression of sensory receptors and cell-surface proteins regulating synaptic target specificity provides a simple and general mechanism for ensuring that transmission of sensory information is processed by the appropriate specialized neural circuits.

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Change history

  • 11 December 2008

    The AOP version of Figure 2 contained errors; these were corrected for print on 11 December 2008.


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We thank Y. N. Jan, H. J. Bellen, A. Nose, S. Britt, C. Desplan, T. Cook, U. Banerjee, the Developmental Studies Hybridoma Bank and Bloomington Stock Center for reagents; H. Schjerven, S. T. Smale and M. Carey for advice and assistance with gel-shift assays; and members of the Zipursky laboratory for comments on the manuscript. S.L.Z. is an investigator of the Howard Hughes Medical Institute. M.M. was supported by the Howard Hughes Medical Institute. S.K.Y. was supported by the Ruth L. Kirschstein National Research Service Award GM7185. T.H. was supported by the Burroughs Wellcome Fund for Biomedical Research. A.N. was supported by the European Molecular Biology Organization and the Human Frontiers Science Program. E.B. was supported by Juan de la Cierva postdoctoral contract and the grant BMC2006-07334 from the Ministerio de Educación y Ciencia (MEC), Spain.

Author Contributions M.M., S.K.Y. and S.L.Z. conceived the experiments and wrote the paper. M.M. and S.K.Y. performed all the experiments. The X-chromosome mosaic screen was designed and performed by T.H. and A.N. E.B. performed all computational sequence analysis.

Author information

Author notes

    • Marta Morey
    •  & Susan K. Yee

    These authors contributed equally to this work.

    • Tory Herman

    Present address: Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, USA.


  1. Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA

    • Marta Morey
    • , Susan K. Yee
    • , Tory Herman
    • , Aljoscha Nern
    •  & S. Lawrence Zipursky
  2. Departament de Genètica and Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, 08028 Barcelona, Catalunya, Spain

    • Enrique Blanco


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Corresponding author

Correspondence to S. Lawrence Zipursky.

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    Supplementary Information

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