The Journal of Neuroscience, July 15, 2002, 22(14):5966-5981
Intrinsic Program for Migration of Cerebellar Granule Cells
In Vitro
Elina
Yacubova and
Hitoshi
Komuro
Department of Neurosciences, Lerner Research Institute, The
Cleveland Clinic Foundation, Cleveland, Ohio 44195
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.
Key words:
cerebellar development; granule cell; neuronal cell
migration; confocal microscopy; microexplant culture and rate of cell
movement; inherent behavior
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