During central nervous system (CNS) development, attractive and repulsive signals guide growing axons to their targets, with many axons having to cross the CNS midline to establish proper connections. Proteins of the Netrin family provide an attractive signal to neurons at the midline, which is relayed by Frazzled/DCC receptors. Now, Thomas Kidd and colleagues report that the Down syndrome cell adhesion molecule (Dscam), previously described as functioning in neurite repulsion and implicated in the neurological aspects of Down syndrome, also guides axons in response to Netrin (see ). The authors show that Netrin and Dscam mutant Drosophila larvae have similar axon guidance defects in their photoreceptor organs, and that Dscam and Netrin physically interact in vitro. By using knockout and overexpression approaches, they demonstrate that Dscam promotes axon midline crossing and acts in parallel to Frazzled/DCC, probably by responding to ligands other than Netrin. From their findings, the authors propose that Dscam transduces several different axonal guidance cues, most likely by associating with co-receptors.
