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Axon routing across the midline controlled by the Drosophila Derailed receptor

Abstract

In nervous systems with symmetry about the midline, many neurons project axons from one side to the other. Although several of the components controlling midline crossing have been identified1,2,3,4, little is known about how axons choose the appropriate pathway when crossing. For example, in the Drosophila embryo axons cross the midline in one of two distinct tracts, the anterior or posterior commissure (AC or PC, respectively). Here we show that the Derailed (Drl) receptor tyrosine kinase is expressed by neurons that project in the AC, and that in the absence of Drl such neurons often project abnormally into the PC. Conversely, misexpression of Drl in PC neurons forces them to cross in the AC. The behaviour of Drl-misexpressing neurons and the in vivo binding pattern of a soluble Drl receptor probe indicate that Drl acts as a guidance receptor for a repellent ligand present in the PC. Our results show that Drl is a novel component in the control of midline crossing.

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Figure 1: Drl is required for proper projection of anterior commissure axons across the midline.
Figure 2: Drl switches axons from the PC to the AC.
Figure 3: Drl recognizes a repulsive cue in the PC.

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Acknowledgements

We thank T. Isshiki, G. Technau, C. Goodman, C. Klämbt and the Indiana Drosophila Stock Center for stocks, and G. Lemke and members of the Thomas lab for helpful comments. This work was supported by funds from the UC San Diego MSTP program to J.L.B., an HFSP Long-Term Fellowship to S.Y. and grants from the NIH to J.B.T.

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Correspondence to John B. Thomas.

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Bonkowsky, J., Yoshikawa, S., O'Keefe, D. et al. Axon routing across the midline controlled by the Drosophila Derailed receptor. Nature 402, 540–544 (1999). https://doi.org/10.1038/990122

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