Slit-Robo signaling during early and late embryogenesis and within axon tracts.

<p>(A): The Slit-Robo signaling during early neurogenesis specifies the initial position of longitudinal tracts. Robo1 is present in growth cones that give rise to the M-tract, Robo1, and Robo3 in growth cones of the I-tract, and Robo1, Robo2, and Robo3 in growth cones of the L-tract. These growth cones project towards the midline where they encounter Slit. The combined strength of Robo-Slit interaction specifies the lateral position of each tract: the L-tract growth cones, because of the highest amounts of Robo proteins and, the strongest Robo-Slit effect, occupy the lateral-most position. The M-tract growth cones, because of the lowest levels of Robo (only Robo1), occupy a position closest to the midline. The I-tract growth cones, with Robo greater than the M but less than the L, occupy a middle position. (B): The Slit-Robo signaling maintains axon tracts in their position from the midline and between tracts after their guidance. The secreted Slit from the midline is transported along the commissural tracts to the longitudinal connectives (which are composed of both the longitudinal tracts and commissural tracts). Slit then gets distributed along or adjacent to the M, I, and L-tracts. The Slit and Slit-N are bound loosely to the ECM of commissural tracts and interacts with Robo in the adjacent longitudinal tracts. This Robo-Slit interaction in tracts maintains the fasciculation of individual axons within tracts and the position of tracts between each other and from the midline. By maintaining inter-tract position within the connectives, Slit-Robo also maintains their position away from the midline as tracts are unable to move from their position. These results suggest that the tracts have a default position and that default position is at the midline.