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. Since the hem expresses multiple Wnt genes, we examined whether β-CATENIN, which mediates canonical Wnt signaling and also participates in cell adhesion, is necessary for the development of hem-derived lineages. We report that the fimbrial glial scaffold is disorganized and CR cells are mispositioned upon hem-specific disruption of β-CATENIN. Consequently, the dentate migratory stream is severely affected, and the dentate gyrus fails to form. Using selective Cre drivers, we further determined that β-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 β-CATENIN for the organization of the fimbrial scaffold and a secondary role for this factor in dentate gyrus morphogenesis. ### Competing Interest Statement MJH is the Founder and President of NuPeak Therapeutics and a member of the Data Safety Monitoring Board for AstraZeneca. All other authors declare no competing interests.