New Roundabouts Send Axons into the Fas Lane

and Flanagan, 1999). This repellent (Slit) and its receptors (Roundabouts) are members of protein families conserved from worm and fly to man. Like Netrins, Slit Even in an invertebrate central nervous system (CNS) proteins are expressed by midline cells, whereas Round-far simpler that our own, axon pathways that connect about (Robo) proteins are found on axons either before the different parts of an organism are tremendously they reach the midline or after they cross, but not during complicated. Despite this complexity, each axon navi-the passage. Like other axon repellents, Slits mediate gates with astonishing precision to reach specific target growth cone collapse. cells. Like mariners at sea, axons require landmarks for Although this work identified Drosophila Slit as the guidance. There are long-range cues that define direc-midline barrier, significant mysteries remained. The ef-tion, like the earth's magnetic field, and short-range fect of Slit loss is different from that of Robo loss. In robo cues that indicate local position, like the islands and mutants, ipsilateral and contralateral axons proximal to coastline on a familiar map. Since different axons have the midline cross and recross the midline indiscrimi-distinct destinations, each axon must interpret this infor-nately. However, in slit mutants, all axons collapse into mation and make decisions appropriate for its destiny. the midline and never escape. This suggests that Robo Although axon guidance has fascinated biologists for is only required at short range in proximal axons to a century, only recently have molecules that specify prevent crossing, but not for escape from the midline, guidance choices been identified (reviewed by Tessier-whereas Slit is required at long range for the guidance Lavigne and Goodman, 1996). We now know that guid-of all axons, and it also mediates escape. This disparity ance is achieved through combinations of factors that predicted some additional Slit receptor(s). The existence act to attract or repel axonal growth cones, and we are of multiple Robo genes in fly and man provided candi-beginning to understand the larger organizing principles dates for this role. that shape neural architecture. Four papers in this Robo2 Fills the Gap month's issues of Cell and Neuron provide a beautiful There are three Robos in Drosophila (Figure 1B). All example of this (Rajagopalan et al., 2000a, 2000b; Simp-three proteins are expressed on axon pathways and are son et al., 2000a, 2000b). Parallel studies from the labo-excluded from the midline barrier. However, only Robo ratories of Corey Goodman …