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

Neural receptor-linked protein tyrosine phosphatases (RPTPs) are required f or guidance of motoneuron and photoreceptor growth cones in Drosophila. The se phosphatases have not been implicated in growth cone responses to specif ic guidance cues, however, so it is unknown which aspects of axonal pathfin ding are controlled by their activities, Three RPTPs, known as DLAR, DPTP69 D, and DPTP99A, have been genetically characterized thus far. Here we repor t the isolation of mutations in the fourth neural RPTP, DPTP10D, The analys is of double mutant phenotypes shows that DPTP10D and DPTP69D are necessary for repulsion of growth cones from the midline of the embryonic central ne rvous system, Repulsion is thought to be triggered by binding of the secret ed protein Slit, which is expressed by midline glia, to Roundabout (Robo) r eceptors on growth cones. Robe repulsion is downregulated by the Commissure less (Comm) protein, allowing axons to cross the midline, Here we show that the Rptp mutations genetically interact with robe, slit and comm. The natu re of these interactions suggests that DPTP10D and DPTP69D are positive reg ulators of Slit/Roundabout repulsive signaling. We also show that eliminati on of all four neural RPTPs converts most noncrossing longitudinal pathways into commissures that cross the midline, indicating that tyrosine phosphor ylation controls the manner in which growth cones respond to midline signal s.