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Bi-directional signaling by Semaphorin 1a during central synapse formation in Drosophila

Abstract

Semaphorins have been intensively studied for their role in dendritic and axonal pathfinding, but less is known about their potential role in synapse formation. In the adult giant fiber (GF) system of fruit flies (Drosophila melanogaster), we show that transmembrane Semaphorin 1a (Sema-1a) is involved in synapse formation in addition to its role in guidance during pathfinding. Cell-autonomous rescue experiments showed that Sema-1a is involved in assembly of a central synapse and that it is required both pre- and postsynaptically. We also found that pre- but not postsynaptic gain-of-function Sema-1a was able to disrupt the GF–motor neuron synapse and that the phenotype depended on a proline-rich intracellular domain that contains a putative Enabled binding site. We suggest that transmembrane Sema-1a is part of a bi-directional signaling system that leads to the formation of the GF synapse and possibly acts as both a ligand and a receptor.

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Figure 1: Developmental expression pattern of Sema-1a in pupae and adults.
Figure 2: Sema-1a loss-of-function disrupts the GF structure.
Figure 3: Sema-1a loss-of-function disrupts the physiology of the GF circuit.
Figure 4: Sema-1a gain-of-function disrupts GF structure.

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Acknowledgements

We thank A. Kolodkin for providing UAS–semaWT, UAS–semaEC and Sema-1a antisera, the J. Bacon and J. Davies labs for the shakB(lethal)–Gal4 line, P. Carrucio, D. Thurman and C. Uemura for technical assistance, and S. Uthaman for critically reading the manuscript. This work was supported by National Science Foundation grant IBN9904957 and National Institutes of Health grant NS44609 to R.K.M., a Howard Hughes Medical Institute predoctoral fellowship to H.H., and National Institutes of Health grant NS18366 and Christopher Reeve Paralysis Foundation grant GBC1-9801-2 to C.S.G.

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Correspondence to Rodney K. Murphey.

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Godenschwege, T., Hu, H., Shan-Crofts, X. et al. Bi-directional signaling by Semaphorin 1a during central synapse formation in Drosophila. Nat Neurosci 5, 1294–1301 (2002). https://doi.org/10.1038/nn976

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