The dentate gyrus is the chief route of excitatory input into the hippocampal formation and is thus crucial for appropriate function of the hippocampus in learning and memory. Many pathological states associated with histological abnormalities

The dentate gyrus is the chief route of excitatory input into the hippocampal formation and is thus crucial for appropriate function of the hippocampus in learning and memory. Many pathological states associated with histological abnormalities in the dentate are likely to have their origins during development. These disorders include generalized abnormalities of neuronal migration, e.g. reeler and associated mutants (Frotscher, 1998; Stanfield and Cowan, 1979a; Stanfield and Cowan, 1979b), and defects that are more restricted to the dentate gyrus, e.g. humans with temporal lobe epilepsy with apparent migration abnormalities of dentate granule neurons (Houser, 1990; Houser et al., 1992). It is now clear that the dentate gyrus is one of the few sites in the rodent brain that undergoes continued neurogenesis throughout life with continued production of granule cell neurons from precursor cells that reside at the border between the dentate granule cell layer and the hilus (the subgranular zone – SGZ) (Altman and Bayer, 1990a; Altman and Das, 1965a; Gage, 2000; Pleasure et al., 2000b). Recent experiments have shown that dentate granule cell neurogenesis is increased by physical activity and the performance of learning paradigms and that continued dentate neurogenesis is likely to be necessary for the ability to perform specific types of learning tasks (Gould et al., 1999; Kempermann et al., 1997; Shors et al., 2001; van Praag et al., 1999). During development, an important event in the formation of the dentate granule cell layer is the migration of cells from the dentate neuroepithelium to take up residence in the dentate gyrus anlage. Traditional neuroanatomical methods have shown that the early stages of migration consist of a mixture of postmitotic neurons and precursor cells that form the primary dentate granule cell layer and populate the hilus (Altman and Bayer, 1990a; Altman and Bayer, 1990b; Pleasure et al., 2000b). As development proceeds, the precursor cells in the hilus proliferate and produce large numbers of granule cells through the first month of postnatal life before settling in the SGZ and gradually reducing their output of new granule cells to a lower basal rate through adulthood (Altman and Bayer, 1990a; Altman and Bayer, 1990b; Altman and Das, 1965a; Altman and Das, 1965b; Pleasure et al., 2000b). We have been examining factors that regulate the development of the dentate granule cell lineage in order to better understand the developmental organizing principles that govern the initial migration of granule cells to the dentate gyrus. As part of these studies, we have become particularly interested in the regulation of the initial migration of cells that 4249 Development 129, 4249-4260 (2002) Printed in Great Britain © The Company of Biologists Limited 2002 DEV9853