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Temporal identity in axonal target layer recognition

Abstract

The segregation of axon and dendrite projections into distinct synaptic layers is a fundamental principle of nervous system organization and the structural basis for information processing in the brain1. Layer-specific recognition molecules that allow projecting neurons to stabilize transient contacts and initiate synaptogenesis2,3 have been identified. However, most of the neuronal cell-surface molecules critical for layer organization are expressed broadly in the developing nervous system4,5, raising the question of how these so-called permissive adhesion molecules support synaptic specificity. Here we show that the temporal expression dynamics of the zinc-finger protein sequoia is the major determinant of Drosophila photoreceptor connectivity into distinct synaptic layers. Neighbouring R8 and R7 photoreceptors show consecutive peaks of elevated sequoia expression, which correspond to their sequential target-layer innervation. Loss of sequoia in R7 leads to a projection switch into the R8 recipient layer, whereas a prolonged expression in R8 induces a redirection of their axons into the R7 layer. The sequoia-induced axon targeting is mediated through the ubiquitously expressed Cadherin-N cell adhesion molecule. Our data support a model in which recognition specificity during synaptic layer formation is generated through a temporally restricted axonal competence to respond to broadly expressed adhesion molecules. Because developing neurons innervating the same target area often project in a distinct, birth-order-dependent sequence, temporal identity seems to contain crucial information in generating not only cell type diversity during neuronal division6 but also connection diversity of projecting neurons.

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Figure 1: Mutations in sequoia disrupt synaptic-layer selection of R8 and R7 axons.
Figure 2: Transient expression of sequoia in projecting R cells.
Figure 3: Temporal control of R8/R7 axon targeting by sequoia.
Figure 4: sequoia -induced temporal targeting competence is mediated via Cadherin-N.

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Acknowledgements

We thank H. Bellen, J. Brenman, I. Salecker and R. Schuh for fly stocks and antibodies; D. Hawellek for the identification and analysis of seq6; and H. Aberle, S. Bogdan, C. Klämbt, A. Püschel and members of the Hummel laboratory for critical comments on the manuscript. T.H. is supported by the Deutsche Forschungsgemeinschaft (SFB629) and the EMBO Young Investigator Programme.

Author Contributions M.P. designed and performed all the experiments, and M.P. and T.H. wrote the manuscript.

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Correspondence to Thomas Hummel.

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Petrovic, M., Hummel, T. Temporal identity in axonal target layer recognition. Nature 456, 800–803 (2008). https://doi.org/10.1038/nature07407

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