[SY3.1]: Self‐avoidance mediated by DSCAM in the developing mammalian retina

During the development of the vertebrate retina, neurons establish both a vertical and lateral organization, which provides the anatomical basis for functional circuitry. Retinal neurons establish their 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 excluded. The lateral mosaics of distinct cell types form independently and can overlap. The molecular cues that direct these processes in the vertebrate retina are not known. We have shown that some types of retinal amacrine cells from mice with a spontaneous mutation in Dscam, a gene encoding an Igsuperfamily member adhesion molecule, have defects in the arborization of processes and 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. The cell bodies of these neurons are randomly distributed or pulled into clumps rather than being spaced in regular mosaics. Our results indicate that mouse DSCAMmediates isoneuronal self-avoidance for arborization, and heteroneuronal self-avoidance within specific cell types to prevent fasciculation and to preserve mosaic spacing. These functions are highly analogous to those of Drosophila Dscam and Dscam2, and are necessary for establishing orderly retinal circuitry. DSCAM may serve a similar role in other regions of the mammalian central nervous system, and this function may be shared by other members of the Dscam gene family.