  Hippocampal dentate granule cells are among the few neuronal cell types
generated throughout adult life in mammals. In the normal brain, new granule
cells are generated from progenitors in the subgranular zone and integrate in a
typical fashion. During the development of epilepsy, granule cell integration
is profoundly altered. The new cells migrate to ectopic locations and develop
misoriented basal dendrites. Although it has been established that these
abnormal cells are newly generated, it is not known whether they arise
ubiquitously throughout the progenitor cell pool or are derived from a smaller
number of bad actor progenitors. To explore this question, we conducted a
clonal analysis study in mice expressing the Brainbow fluorescent protein
reporter construct in dentate granule cell progenitors. Mice were examined 2
months after pilocarpine-induced status epilepticus, a treatment that leads to
the development of epilepsy. Brain sections were rendered translucent so that
entire hippocampi could be reconstructed and all fluorescently labeled cells
identified. Our findings reveal that a small number of progenitors produce the
majority of ectopic cells following status epilepticus, indicating that either
the affected progenitors or their local microenvironments have become
pathological. By contrast, granule cells with basal dendrites were equally
distributed among clonal groups. This indicates that these progenitors can
produce normal cells and suggests that global factors sporadically disrupt the
dendritic development of some new cells. Together, these findings strongly
predict that distinct mechanisms regulate different aspects
