Cas Adaptor Proteins Organize the Retinal Ganglion Cell Layer Downstream of Integrin Signaling

Stratification of retinal neuronal cell bodies and lamination of their processes provide a scaffold upon which neural circuits can be built. However, the molecular mechanisms that direct retinal ganglion cells (RGCs) to resolve into a single-cell retinal ganglion cell layer (GCL) are not well understood. The extracellular matrix protein laminin conveys spatial information that instructs the migration, process outgrowth, and reorganization of GCL cells. Here, we show that the beta 1-Integrin laminin receptor is required for RGC positioning and reorganization into a single-cell GCL layer. beta 1-Integrin signaling within migrating GCL cells requires Cas signaling-adaptor proteins, and in the absence of beta 1-Integrin or Cas function retinal neurons form ectopic cell clusters beyond the inner-limiting membrane (ILM), phenocopying laminin mutants. These data reveal an essential role for Cas adaptor proteins in beta 1-Integrin-mediated signaling events critical for the formation of the single-cell GCL in the mammalian retina.