Partial Deletion of Cxcl12 from Hippocampal Cajal–Retzius Cells Does Not Disrupt Dentate Gyrus Development or Neurobehaviors

The chemokine CXCL12 plays critical roles in the development of the hippocampus dentate gyrus during both embryogenesis and adulthood. While multiple cell types in the hippocampus express Cxcl12 , their individual contributions to the dentate gyrus development and function remain unclear. Here, using Cxcl12 reporter mice of both sexes, we characterize Cxcl12 expression in Cajal–Retzius (CR) cells—neurons that guide dentate gyrus morphogenesis and influence hippocampal circuitry. We show that CR cells prominently express Cxcl12 during early postnatal development, although both the number and proportion of Cxcl12 -expressing CR cells decline significantly in adulthood. Notably, partial deletion of Cxcl12 from hippocampal CR cells in male and female mice does not result in detectable changes in dentate gyrus architecture, adult neurogenesis, or specific behaviors. These findings suggest that CR cell-derived CXCL12 may be less critical for dentate gyrus development than previously assumed and underscore the complexity and potential redundancy of CXCL12 signaling in the hippocampus.