Intrinsic program for migration of cerebellar granule cells in vitro

Cerebellar granule cells exhibit distinct modes of migration in different cortical layers. The role of external cues in controlling these alterations has been suggested, but the significance of internal programs is not well understood. In the present study, we examined autonomous changes of migratory behavior of isolated granule cells in microexplant cultures of the postnatal mouse cerebellum. We found that isolated granule cells sequentially go through three characteristic phases of migration without cell-cell contact. In the first phase (0-20 hr in vitro) granule cells exhibit the highest rate of turning behavior and have multiple short processes. The length of the movement cycle is shortest. In the second phase (20-40 hr in vitro), granule cells extend a long and thick process and exhibit an elongated cycle of movement. Their speed is fastest, whereas the rate of turning is lowest. In the third phase (40-60 hr in vitro), granule cells slow down their movement and slightly increase their turnings. The length of the movement cycle further increases. At the end, the cells become permanently stationary, extend a lamellipodium around the soma, and emit several thin processes. Interestingly, granule cells sequentially develop four different modes of turning. These results indicate that internal (intrinsic) programs control alterations of granule cell behavior in a stage-dependent manner, suggesting that such programs independent of local cell-cell contacts may be essential for granule cell translocation in the developing cerebellum.