Downs syndrome cell adhesion molecules (Dscams) are adhesion molecules of the immunoglolulin superfamily. Drosophila Dscams have been implicated in the organization of neural connectivity, but little is known about the functions of the closely related molecules in vertebrates. Masahito Yamagata and Joshua Sanes now demonstrate a role for Dscam and DscamL in patterning of lamina-specific connections in the chick retina. Two other adhesion molecules, called Sidekick-1 and Sidekick-2, act in a similar way. These molecules are widely distributed in the nervous system and may be part of an 'adhesive code' that patterns neural connections in the brain. Further evidence for the importance of Dscams in vertebrate neural patterning comes from Fuerst et al., who identify a role for DSCAM in establishing neural circuits in the retina of mice. In establishing circuits in the retina, retinal neurons form complex patterns depending on repulsion or attraction to their own processes, and to the cell bodies and processes of other neurons. The first cell surface adhesive protein that mediates this cell spacing in the mammalian retinal is described. This paper also identifies a spontaneous mutation in mice that creates a loss of function allele of Dscam, which in Drosophila mediates dendrite arborization and axon tiling, and finds the mutants eyes had disorganized retinas with faulty cell spacing. To establish functional circuitry, retinal neurons occupy spatial domains by arborizing their processes, which requires the self-avoidance of neurites from an individual cell, and by spacing their cell bodies, which requires positioning the soma and establishing a zone within which other cells of the same type are excluded1. The mosaic patterns of distinct cell types form independently and overlap. The cues that direct these processes in the vertebrate retina are not known2,3. Here we show that some types of retinal amacrine cells from mice with a spontaneous mutation in Down syndrome cell adhesion molecule (Dscam), a gene encoding an immunoglobulin-superfamily member adhesion molecule4,5, have defects in the arborization of processes and in the spacing of cell bodies. In the mutant retina, cells that would normally express Dscam have hyperfasciculated processes, preventing them from creating an orderly arbor. Also, their cell bodies are randomly distributed or pulled into clumps rather than being regularly spaced mosaics. Our results indicate that mouse DSCAM mediates isoneuronal self-avoidance for arborization and heteroneuronal self-avoidance within specific cell types to prevent fasciculation and to preserve mosaic spacing. These functions are analogous to those of Drosophila DSCAM (ref. 6) and DSCAM2 (ref. 7). DSCAM may function similarly in other regions of the mammalian nervous system, and this role may extend to other members of the mammalian Dscam gene family.