Cell migration in cultured cerebral cortical slices.

In order to investigate the cellular mechanisms of migration and lamination in the mammalian cerebral cortex, we have cultured living slices of the developing telencephalon and tracked the migration of newly generated cortical neurons. Slice cultures made from neonatal ferret cortex were maintained in roller tubes and survived well for several weeks in vitro. Cells generated on Postnatal Day (P) 0 or 1 were labeled with the thymidine analog 5-bromo-2-deoxy-uridine (BrdU), and their movements were tracked during the subsequent culture period. At the beginning of the culture period, labeled cells were found almost exclusively in the proliferative zones of the cerebral wall, the ventricular and subventricular zones. Over the first week in culture, there was a dramatic movement of labeled cells out of the proliferative zones and into the cortical plate, the final destination of neocortical neurons. Comparison of the patterns of cell movement in cultured slices with that in intact littermate controls revealed that the initial migration of labeled cells into the cortical plate is similar in cultured slices and normal animals. The primary difference between migration in slice cultures and in vivo is that after longer times in culture, cells that migrate into the cortical plate fail to form the tightly clustered laminae characteristic of cells in the intact brain. Labeled cells are instead distributed more widely throughout the cortical plate and other regions of the cerebral wall. Thus, at least during the initial period of migration, cultured slices provide an experimentally manipulable system in which cell migration can be directly observed in a histotypically normal environment.