Differential contribution of P73+ Cajal-Retzius cells and Reelin to cortical morphogenesis

Cajal-Retzius cells (CRs) are a peculiar neuronal type within the developing mammalian cerebral cortex. One of their best documented feature is the robust secretion of Reln, a glycoprotein essential for the establishment of cortical layers through the control of radial migration of glutamatergic neurons. Although CRs and Reln are tightly associated, a direct assessment of their relative contribution to cortical morphogenesis is still lacking. Here we took advantage of the Gmnc-/- mouse model, in which CRs are initially produced but abnormally specified and undergo early apoptosis leading to a severe depletion, to investigate the consequences of CRs loss on neocortical lamination and hippocampal morphogenesis. We then compared to the phenotype of CRs-specific conditional Reln deletion in order to evaluate the relative contribution of CRs and Reln. We found that neocortical lamination defects upon CRs depletion are relatively modest, and partially recapitulated by Reln loss. By contrast, hippocampal morphogenesis was far more affected by CRs depletion than Reln loss. In addition, we found the lateral cortex especially sensitive to CRs depletion, but not Reln loss. These data support a model whereby CRs-derived Reln and Reln-independent signals differentially contribute to the morphogenesis of distinct regions of the developing cortex. The forebrain of four Gmnc-/- P0 animals originating from two distinct litters and four wild-type littermates were collected. The region encompassing the lateral and dorsal cortex as well as the hippocampus was dissected on both hemispheres and samples were pooled according to their genotype. Cells were dissociated and two Next GEM Single Cell 3’ v3.1 libraries were produced (one per genotype).