Sema3C and Netrin-1 Differentially Affect Axon Growth in the Hippocampal Formation

The interaction between outgrowing neurons and their targets is a central element in the development of the afferent and efferent connections of the hippocampal system. This requires that axonal growth cones recognize specific guidance cues in the appropriate target area. At present, little is known about the mechanisms that determine the lamina-specific termination of hippocampal afferents. In order to understand the role of different guidance factors, we analyzed the effects of Sema3C and Netrin-1 on explants from the entorhinal cortex, dentate gyrus, cornu ammonis regions CA1 and CA3 and medial septum in a collagen coculture assay. Our observations suggest that both semaphorins and netrin play important roles in the neuron–target interactions in the hippocampal system. Sema3C is involved in the control of the ingrowth of the septohippocampal projection. We also show that netrin-1 is involved in attracting commissural neurons from dentate gyrus/hilus and CA3 to their target area in the contralateral hippocampus.