The development and integration of neurons into neural tissues is mediated by cell adhesion molecules, whose different specificities encode circuit architecture and connectivity. While neurons require adhesive cues to identify and interact with potential synaptic partners, repulsive cues are also required to prevent neurons from becoming entangled in their own processes or with the processes of like cells. In Drosophila , the Down Syndrome Cell Adhesion Molecule (DSCAM) family provides these repulsive cues, in part mediated by the amazing splice diversity of Drosophila Dscam1 . Drosophila Dscams are also required for several other processes, including axon guidance and synaptic specificity. While vertebrate Dscams lack the splice diversity observed in Drosophila Dscam1 , they retain similar functions. Recent work focusing in the retina of both mouse and chick has identified roles for DSCAM proteins in repulsive avoidance and neurite lamination. The study by Fuerst et al. in this issue extends this work, first by identifying a new mutant mouse allele of Dscam and then by confirming that laminar disorganization observed in the DSCAM‐depleted chick retina is also observed in some populations of amacrine cells in the Dscam null mouse retina. Previous studies using mutant mouse alleles of Dscam were complicated by the postnatal lethality of Dscam mutant mice on an inbred C57Bl/6 background, as well as the associated genetic diversity experimentally introduced to promote survival. The Dscam null allele used in this study was viable on the inbred C3H strain on which it arose, allowing phenotypes in the postnatal Dscam mutant retina to be assayed in the absence of genetic variability. The availability of a mutant allele of Dscam on an inbred background allowed retinal neurite lamination to be further examined. A lamination defect was observed in two populations of amacrine cells, indicating that DSCAM's role in neurite lamination is conserved across vertebrates. Interestingly, the calbindinpositive amacrine cells were sensitive to background effects, having grossly disorganized lamination on a C3H background but maintaining a fasciculated lamination on a mixed C57BL/6‐Balb background. Many challenges remain with respect to understanding how the multiple functions DSCAM proteins contribute to neural development. Current limitations include a lack of reliable antibody reagents with which protein localization can be monitored. Another challenge is to determine which Dscam ‐mutant phenotypes are primary and which are downstream effects. For example, retinal ganglion cells are highly disorganized and have clumped dendrites as early as late prenatal stages. Defects observed in amacrine cell neurite lamination may therefore reflect either a primary defect of amacrine cell lamination or a secondary result of amacrine cell neurites colaminating with disorganized retinal ganglion cell processes. Fortunately new resources, such as the strain presented here will allow these questions to be better addressed.

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