Reelin and mDab1 regulate the development of hippocampal connections

We analyze in this study the participation of Reelin and mDab1 in the development of hippocampal connections. We show that mDab1 is present in growth cones and axonal tracts of developing hippocampal afferents. mdab1-deficiency produces severe alterations in the entorhino-hippocampal and commissural connections identical to those described in reeler mice, including innervation of ectopic areas, formation of abnormal patches of fiber termination and a delay in the refinement of projections. Organotypic slice cultures combining tissue from mdab1-mutant and control mice demonstrate that the abnormalities observed in the mutant entorhino-hippocampal projection are caused by mdab1-deficiency in both the projecting neurons and target hippocampal cells. Axonal afferents that innervate the hippocampus react to Reelin by reducing axonal growth, and increasing growth cone collapse and axonal branching. Altogether these results indicate that Reelin and mDab1 participate in the development and refinement of hippocampal connections by regulating axonal extension, targeting and branching.