This chapter deals with the laminated organization of the dentate gyrus, particularly with the molecular signals controlling its development. First, sites of granule cell generation, their modes and routes of migration are described. This is followed by an analysis of the molecular determinants governing the formation of a tightly packed granule cell layer that is normal in rodents and primates. Reelin, a protein of the extracellular matrix, plays an important role for the proper migration and lamination of the granule cells during development and for the maintenance of a laminated dentate gyrus in adulthood. Granule cell positioning is crucial for the laminated termination of commissural/associational fibers to the dentate gyrus, suggesting that the granule cells carry positional signals for these fibers. In contrast, not signals of the target cells but molecules of the extracellular matrix, such as hyaluronan, underlie the layer-specific termination of fibers from the entorhinal cortex. The molecular determinants controlling axonal pathfinding and target recognition of the profusely terminating cholinergic and GABAergic subcortical afferents still need to be elucidated.
