Development of the hippocampal formation in mutant mice

The highly laminated structures of the hippocampal formation provide an ideal location for the assessment of the effects of mutant genes on the development of the central nervous system. Presently seven different mutations and one genetic variant (NZB/BINJ) are known to affect the developing hippocampal formation. Each of them affects neuronal migration and/or cell proliferation in a different constellation of cell types and produces a distinct pattern of reorganization. The fact that different mutations, which map to different chromosomal locations, can affect neuronal migration in the hippocampal formation indicates that there is a variety of developmental processes that influence the ultimate destination of a migrating neuron. In addition, the fact that the different mutations do not uniformly affect all populations of migrating cells indicatesd that, in some cases, migrating neurons with different destinations may use different cues to find their final position. Conversely, the overlap in the phenotypes of the various mutations provides insight into the extent of common gene expression during neuronal migration. For example, six of the mutations have ectopic CA3 pyramidal cells. These same six mutations also have ectopic granule cells in the molecular layer of the cerebellar cortex. This association may reflect the existence of common gene expression during the migration of these two diverse cell types. Also, NZB/BINJ mice and four of the single gene mutations have immune system dysfunctions. Thus, there may be common gene expression during the differentiation of the immune system and neuronal migration. These genetic tools provide a significant new way to explore cerebral cortical development, in general, and neuronal migration, in particular.