The interaction between outgrowing neurons and their targets is a central e
lement in the development of the afferent and efferent connections of the h
ippocampal system. This requires that axonal growth cones recognize specifi
c guidance cues in the appropriate target area. At present, little is known
about the mechanisms that determine the lamina-specific termination of hip
pocampal afferents. In order to understand the role of different guidance f
actors, we analyzed the effects of Sema3C and Netrin-1 on explants from the
entorhinal cortex, dentate gyrus, cornu ammonis regions CAI and CA3 and me
dial septum in a collagen coculture assay. Our observations suggest that bo
th semaphorins and netrin play important roles in the neuron-target interac
tions in the hippocampal system. Sema3C is involved in the control of the i
ngrowth of the septohippocampal projection. We also show that netrin-1 is i
nvolved in attracting commissural neurons from dentate gyrus/hilus and CA3
to their target area in the contralateral hippocampus.