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Published February 15, 2000 | Published
Journal Article Open

Receptor tyrosine phosphatases regulate axon guidance across the midline of the Drosophila embryo


Neural receptor-linked protein tyrosine phosphatases (RPTPs) are required for guidance of motoneuron and photoreceptor growth cones in Drosophila. These phosphatases have not been implicated in growth cone responses to specific guidance cues, however, so it is unknown which aspects of axonal pathfinding are controlled by their activities. Three RPTPs, known as DLAR, DPTP69D, and DPTP99A, have been genetically characterized thus far. Here we report the isolation of mutations in the fourth neural RPTP, DPTP10D. The analysis of double mutant phenotypes shows that DPTP10D and DPTP69D are necessary for repulsion of growth cones from the midline of the embryonic central nervous system. Repulsion is thought to be triggered by binding of the secreted protein Slit, which is expressed by midline glia, to Roundabout (Robo) receptors on growth cones. Robo repulsion is downregulated by the Commissureless (Comm) protein, allowing axons to cross the midline. Here we show that the Rptp mutations genetically interact with robo, slit and comm. The nature of these interactions suggests that DPTP10D and DPTP69D are positive regulators of Slit/Roundabout repulsive signaling. We also show that elimination of all four neural RPTPs converts most noncrossing longitudinal pathways into commissures that cross the midline, indicating that tyrosine phosphorylation controls the manner in which growth cones respond to midline signals.

Additional Information

Copyright © 2000 by Company of Biologists. Accepted 22 November 1999; published on WWW 26 January 2000. We thank the members of the Zinn group for discussions and comments on the manuscript, and Tom Kidd, Julie Simpson, and Corey Goodman for communication of results before publication. This work was supported by a Human Frontiers Science Project grant (RG0122/1997-B) to K. Zinn and W. Chia, and by an NIH RO1 grant to K.Z.

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