Integrity of Cajal-Retzius cells in the reeler-mouse hippocampus

Cajal-Retzius (CR) cells are early-born glutamatergic neurons that are primarily known as the early main source of the signal protein Reelin. In the reeler mutant, the absence of Reelin causes severe defects in the radial migration of neurons, resulting in abnormal cortical layering. To date, the exact morphological properties of CR-cells independent of Reelin are unknown. With this in view, we studied the ontogenesis, density, and distribution of CR-cells in reeler mice that were cross-bred with a CXCR4-EGFP reporter mouse line, thus enabling us to clearly identify CR-cells positions in the disorganized hippocampus of the reeler mouse. As evidenced by morphological analysis, differences were found regarding CR-cell distribution and density: generally, we found fewer CR-cells in the developing and adult reeler hippocampus as compared to the hippocampus of wild-type animals (WT); however, in reeler mice, CR-cells were much more closely associated to the hippocampal fissure (HF), resulting in relatively higher local CR-cell densities. This higher local cell density was accompanied by stronger immunoreactivity of the CXCR4 ligand, stroma-derived factor-1 (SDF-1) that is known to regulate CR-cell positioning. Importantly, confocal microscopy indicates an integration of CR-cells into the developing and adult hippocampal network in reeler mice, raising evidence that network integration of CR-cells might be independent of Reelin.