Complex genetic interactions among four receptor tyrosine phosphatases regulate axon guidance in Drosophila

Four receptor-linked protein tyrosine phosphatases are selectively expressed on central nervous system axons in the Drosophila embryo. Published data show that three of these (DLAR, DPTP69D, DPTP99A) regulate motor axon guidance decisions during embryonic development. Here we examine the role of the fourth neural phosphatase, DPTP10D, by analyzing double-, triple-, and quadruple-mutant embryos lacking all possible combinations of the phosphatases. This analysis shows that all four phosphatases participate in guidance of interneuronal axons within the longitudinal tracts of the central nervous system. In the neuromuscular system, DPTP10D works together with the other three phosphatases to facilitate outgrowth and bifurcation of the SNa nerve, but acts in opposition to the others in regulating extension of ISN motor axons past intermediate targets. Our results provide evidence for three kinds of genetic interactions among the neural tyrosine phosphatases: partial redundancy, competition, and collaboration.