Dentate gyrus morphogenesis is regulated by β-catenin function in hem-derived fimbrial glia

The dentate gyrus, a gateway for input to the hippocampal formation, arises from progenitors in the medial telencephalic neuroepithelium adjacent to the cortical hem. Dentate progenitors navigate a complex migratory path guided by two cell populations that arise from the hem, the fimbrial glia and Cajal-Retzius (CR) cells. As the hem expresses multiple Wnt genes, we examined whether beta-catenin, which mediates canonical Wnt signaling and also participates in cell adhesion, is necessary for the development of hem-derived lineages. We report that, in mice, the fimbrial glial scaffold is disorganized and CR cells are mispositioned upon hem-specific disruption of beta-catenin. Consequently, the dentate migratory stream is severely affected, and the dentate gyrus fails to form. Using selective Cre drivers, we further determined that beta-catenin function is required in the fimbrial glial scaffold, but not in the CR cells, for guiding the dentate migration. Our findings highlight a primary requirement for beta-catenin for the organization of the fimbrial scaffold and a secondary role for this factor in dentate gyrus morphogenesis.

Automated summary

The study reveals the importance of beta-catenin in the development of brain structures, particularly in the formation of the dentate gyrus. In mice, disruption of beta-catenin leads to disorganization of the fimbrial glial scaffold and mispositioning of Cajal-Retzius cells, resulting in the failure of the dentate gyrus to form.