Figure 3.

Molecular cues controlling the pathway choices at the Drosophila and vertebrate midline. (A) Comm regulates Robo1 trafficking and midline crossing. Model for the sorting action of Comm on Robo1; inset to the left shows enlarged view of the boxed region. In an ipsilateral neuron (top), Comm is absent and Robo1 is inserted into the growth cone, ensuring midline repulsion by Slit. In a commissural neuron (middle), Comm is present and diverts Robo1 to the endosomes, making the growth cone insensitive to Slit. After crossing (bottom), Comm is reduced and Robo1 begins to accumulate in the contralateral axon segment, potentially preventing the growth cone from crossing again. (Adapted from Dickson and Gilestro 2006.) (B) The Slit/Robo and Sema3B, 3F/Neuropilin2 systems control midline guidance. Robo3.1 (Rig-1), an inhibitor of Robo1 and 2, is required for commissural axons to cross the midline. In the absence of Robo3.1, no commissural axons are able to cross the floor plate, because Slits in the midline repel commissural axons. After entering the floor plate, commissural axons acquire a repulsive response to Sema3B (in the floor plate), Sema3F (in the ventral spinal cord gray matter) and Slits (in the floor plate and ventral spinal cord gray matter), which turn their trajectory into a longitudinal one. The stem cell factor in the floor plate promotes the growth of commissural axons via the Kit receptor to allow axons to cross the midline in this highly repulsive environment.