RESUMEN
The mammalian cerebral cortex is divided into functionally distinct areas. Although radial patterns of neuronal migration have been thought to be essential for patterning these areas, direct observation of migrating cells in cortical brain slices has revealed that cells follow both radial and nonradial pathways as they travel from their sites of origin 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 neurons may not be confined to radial migratory pathways in vivo. Here, we have examined the patterns of neuronal migration in the intact cortex. Analysis of the orientations of [3H]thymidine-labeled migrating cells suggests that nonradial migration is equally common in brain slices and the intact cortex and that it increases during neurogenesis. Additionally, cells appear to follow nonradial trajectories at all levels of the developing cerebral wall, suggesting that tangential migration may be more prevalent than previously suspected from the imaging studies. Immunostaining with neuron-specific antibodies revealed that many tangentially migrating cells are young neurons. These results suggest that tangential migration in the intact cortex plays a pivotal role in the tangential dispersion of clonally related cells revealed by retroviral lineage studies (Walsh, C. and Cepko, C. L. (1992) Science 255, 434-440). Finally, we examined possible substrata for nonradial migration in dorsal cortical regions where the majority of glia extend radially. Using confocal and electron microscopy, we found that nonradially oriented cells run perpendicular to glial processes and make glancing contacts with them along their leading processes. Thus, if nonradial cells utilize glia as a migratory substratum they must glide across one glial fiber to another. Examination of the relationships between migratory cells and axons revealed axonal contacts with both radial and nonradial cells. These results suggest that nonradial cells use strategies and substrata for migration that differ from those employed by radial cells.
Asunto(s)
Corteza Cerebral/embriología , Hurones/embriología , Neuronas/fisiología , Animales , Autorradiografía , Axones/ultraestructura , Movimiento Celular , Corteza Cerebral/citología , Corteza Cerebral/ultraestructura , Inmunohistoquímica , Microscopía Confocal , Microscopía Electrónica , Neuroglía/ultraestructura , Neuronas/ultraestructuraRESUMEN
The neocortex is patterned in layers of neurons that are generated in an orderly sequence during development. This correlation between cell birthday and laminar fate prompted an examination of how neuronal phenotypes are determined in the developing cortex. At various times after labeling with [3H]thymidine, embryonic progenitor cells were transplanted into older host brains. The laminar fate of transplanted neurons correlates with the position of their progenitors in the cell cycle at the time of transplantation. Daughters of cells transplanted in S-phase migrate to layer 2/3, as do host neurons. Progenitors transplanted later in the cell cycle, however, produce daughters that are committed to their normal, deep-layer fates. Thus, environmental factors are important determinants of laminar fate, but embryonic progenitors undergo cyclical changes in their ability to respond to such cues.