Reduced neuronal self-avoidance in mouse starburst amacrine cells with only one Pcdhg isoform

The clustered protocadherins (cPcdhs) are a family of [~]60 homophilic cell adhesion molecules expressed across three gene clusters (Pcdha, Pcdhb, and Pcdhg) with a variety of essential roles in the developing nervous system. Some of these roles rely on specific isoforms, while others are more consistent with a model of isoform redundancy or a requirement for diversity. The {gamma}-Pcdhs (expressed from the Pcdhg gene cluster) are particularly important for neuronal self-avoidance in starburst amacrine cells in the mouse retina. Here, we used mouse mutants to test two of the C-type isoforms - {gamma}C4 and {gamma}C5 - and found that neither was required for normal self-avoidance. Conversely, when we analyzed a mutant with only {gamma}C4 intact, we found significant failures in self-avoidance that could not be completely rescued by overexpression of this isoform from a transgene. We have recently found that this isoform is essential for normal neuronal survival during development, and our new findings here support the hypothesis that {gamma}C4 is specialized for the survival function at the expense of a significant role in self-avoidance.