Migratory growth cones read guidance cues in both dorso-ventral and antero-posterior axes (e.g. the excretory canals, neuronal axons). The goal of this project is to disover how the many different signals are integrated and translated to the final direction a growth cone follows. The excretory cell is an excellent model to study both A-P and D-V migrations as it sends out 4 projections that make their trajectory along both axes. From the phenotype of
unc-53 mutants, which stop posterior excretory canal outgrowth near the vulva, we know that
unc-53 interferes with antero-posterior growth cone steering.
unc-53 also plays a role in the integration of D-V signals, since mutants with ventral excretory canal outgrowth are strongly enhanced in an
unc-53 background, whereas there is no enhancement of the A-P migration. To identify new components of the pathways involved in the integration of both types of signals, we designed a genetic screen using an
unc-53 mutant. This provides us with a sensitized background to find animals with excretory cells that send out ventral projections. One mutation,
bg2, has no canal phenotype by itself in the
unc-53 background. From the other mutants we isolated, we choose the four with the highest penetrance,
bg4 to
bg7, and are currently analyzing those.