Neuronal migration

A precisely orchestrated cell migration is an integral part of the cortical histogenesis of either the cerebellum or the cerebrum.

Neuronal progenitor cells have simple bipolar morphology and span the width of the tube. They then undergo mitosis with the M phase taking place at the ventricular surface of the neural tube. The post-mitotic immature neurons migrate away from ventricular zone to the margin forming the mantle layer.

Progenitor cells thus undergo a constant up-and-down migration through the stages of cell cycle. This is called interkinetic nuclear migration. The function of this process is unclear, but it is assumed that migration is necessary to provide progenitor cells with specific signals at different times in the cell cycle.

The neurons migrate a short distance to form a distinct layer, just beneath the pial surface known as the preplate.  Neuronal migration

The preplate consists of two distinct cell types:

  • A more superficial marginal zone, containing a group of large, stellate shaped cells, known as Cajal-Retzius cells, and
  • A deeper zone of cells called the subplate.


Figure 5 modified from "Neuroscience 2nd Edition, S. Mark Williams", Fig. 22.6.

New post-mitotic neurons accumulate within the preplate forming the cortical plate. The preplate is thus sub-divided into a superficial marginal zone and an intermediate zone. It also has an increasing number of incoming axons. The cortical neurons migrate primarily in a radial direction.

The preplate and its development are illustrated in Fig. 8


Guiding Migration

Radial glial cells in the cerebrum and Bergmann glial cells in the cerebellum provide a scaffold for migrating neurons.

Long processes extend from the ventricular zone to pial surfaces as shown in electron microscopic studies by Pasko Rakic. These processes help in migration. The radial glial cells disappear after development (whereas Bergmann glia do not).

The process of migration is saltatory, neurons start and stop along the way. Migration also happens inside out, the newly generated neurons migrate past the earlier generated neurons, which are still differentiating.

The leading process pulls the cell bodies towards the pial surface. This is known as somal translocation. It is tangential to the cortical surface. Another mechanism is called chain migration where the SVZ cells of the sub-ventricular (SVZ) slide along one another.

After initial gliogenesis, most postnatal cells in the SVZ of mature rodents migrate to the olfactory bulb. This is known as rostral migratory stream. The astrocytic networks have rostral-caudal orientation. 

Figure 6 modified from "Molecular Biology of the Cell" 4th Ed, Fig 21.93

Figure 7: Migration of neuron, time in seconds.

As Hatten observed in an experiment, adhesion molecules such as TAG1 (tubulin-associated glycoprotein 1), L1 and Astrotactin play a important role in migration of granule cells. Astrotactin resembles other cell adhesion molecules but is, however, a distinct family.

Reelin (localized on chromosome 7q22) is also important for correct migration and is expressed in granule cells of the EGL. In the cerebral cotex, Cajal-Retzius cells express Reelin, which can act either as a chemoattractant or a chemorepellant. Mice with a mutant reelin gene, known as Reeler mice, show signs of ataxia. 

                     Figure 7: Migration of neuron, time in seconds.

                     Modified from "Development of the Nervous System" 2nd Ed, Fig. 3.22.