TANGENTIAL MIGRATION OF NEURONS IN THE DEVELOPING CEREBRAL-CORTEX

The mammalian cerebral cortex is divided into functionally distinct ar eas, Although radial patterns of neuronal migration have been thought to be essential for patterning these areas, direct observation of migr ating cells in cortical brain slices has revealed that cells follow bo th radial and nonradial pathways as they travel from their sites of or igin in the ventricular zone out to their destinations in the cortical plate (O'Rourke, N. A., Dailey, M. E., Smith, S. J. and McConnell, S. K. (1992) Science 258, 299-302), These findings suggested that neuron s may not be confined to radial migratory pathways in vivo, Here, we h ave examined the patterns of neuronal migration in the intact cortex, Analysis of the orientations of [H-3]thymidine-labeled migrating cells suggests that nonradial migration is equally common in brain slices a nd the intact cortex and that it increases during neurogenesis. Additi onally, cells appear to follow nonradial trajectories at all levels of the developing cerebral wall, suggesting that tangential migration ma y be more prevalent than previously suspected from the imaging studies , Immunostaining with neuron-specific antibodies revealed that many ta ngentially migrating cells are young neurons. These results suggest th at tangential migration in the intact cortex plays a pivotal role in t he tangential dispersion of clonally related cells revealed by retrovi ral lineage studies (Walsh, C, and Cepko, C. L, (1992) Science 255, 43 4-440), Finally, we examined possible substrata for nonradial migratio n in dorsal cortical regions where the majority of glia extend radiall y, Using confocal and electron microscopy, we found that nonradially o riented cells run perpendicular to glial processes and make glancing c ontacts with them along their leading processes, Thus, if nonradial ce lls utilize glia as a migratory substratum they must glide across one glial fiber to another, Examination of the relationships between migra tory cells and axons revealed axonal contacts with both radial and non radial cells, These results suggest that nonradial cells use strategie s and substrata for migration that differ from those employed by radia l cells.