Neuronal clustering and fasciculation phenotype in Dscam- and Bax-deficient mouse retinas.

Individual types of retinal neurons are distributed to minimize proximity to neighboring cells. Many of these same cell types extend dendrites to provide coverage of the retinal surface. These two cardinal features of retinal mosaics are disrupted, for certain cell types, in mice deficient for the Down syndrome cell adhesion molecule, Dscam, exhibiting an aberrant clustering of somata and fasciculation of dendrites. The Dscam mutant mouse retina also exhibits excess numbers of these same cell types. The present study compared these two features in Dscam mutant retinas with the Bax knockout retina, in which excess numbers of two of these cell types, the melanopsin-positive retinal ganglion cells (MRGCs) and the dopaminergic amacrine cells (DACs), are also present. Whole retinas were immunolabeled for both populations, and every labeled soma was plotted. For the MRGCs, we found a gene dosage effect for Dscam, with the Dscam+/- retinas showing smaller increases in cell number, clustering, and fasciculation. Curiously, Bax-/- retinas, showing numbers of MRGCs intermediate to those found in the Dscam-/- and Dscam+/- retinas, also had clustering and fasciculation phenotypes that were intermediate to retinas with those genotypes. DACs, by comparison, showed changes in both the Dscam-/- and the Bax-/- retinas that did not correlate with their increases in DAC number. The fasciculation phenotype in the Dscam-/- retina was particularly prominent despite only modest clustering. These results demonstrate that the somal clustering and fasciculation observed in the Dscam mutant retina are not unique to Dscam deficiency and are manifested distinctively by different retinal cell types.