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Hippocampal dentate granule cells are among the few neuronal cell typesgenerated throughout adult life in mammals. In the normal brain, new granulecells are generated from progenitors in the subgranular zone and integrate in atypical fashion. During the development of epilepsy, granule cell integrationis profoundly altered. The new cells migrate to ectopic locations and developmisoriented basal dendrites. Although it has been established that theseabnormal cells are newly generated, it is not known whether they ariseubiquitously throughout the progenitor cell pool or are derived from a smallernumber of bad actor progenitors. To explore this question, we conducted aclonal analysis study in mice expressing the Brainbow fluorescent proteinreporter construct in dentate granule cell progenitors. Mice were examined 2months after pilocarpine-induced status epilepticus, a treatment that leads tothe development of epilepsy. Brain sections were rendered translucent so thatentire hippocampi could be reconstructed and all fluorescently labeled cellsidentified. Our findings reveal that a small number of progenitors produce themajority of ectopic cells following status epilepticus, indicating that eitherthe affected progenitors or their local microenvironments have becomepathological. By contrast, granule cells with basal dendrites were equallydistributed among clonal groups. This indicates that these progenitors canproduce normal cells and suggests that global factors sporadically disrupt thedendritic development of some new cells. Together, these findings stronglypredict that distinct mechanisms regulate different aspects

Clonal analysis of newborn hippocampal dentate granule cell proliferation and development in temporal lobe epilepsy