Crossing the midline: Roles and regulation of robo receptors

In the Drosophila CNS, the midline repellent Slit acts at short range through its receptor Robe to control midline crossing. Longitudinal axons express high levels of Robe and avoid the midline; commissural axons that cross the midline express only low levels of Robe. Robe levels are in turn regulated by Comm. Here, we show that the Slit receptors Robo2 and Robo3 ensure the fidelity of this crossing decision: rare crossing errors occur in both robo2 and robo3 single mutants. In addition, low levels of either Robo or Robo2 are required to drive commissural axons through the midline: only in robo,robo2 double mutants do axons linger at the midline as they do in silt mutants. Robo2 and Robo3 levers are also tightly regulated, most likely by a mechanism similar to but distinct from the regulation of Robe by Comm.