Cerebrum - development

Cerebral cortex histogenesis

The cerebral hemispheres develop from the wall of the telencephalic vesicle.

Neuroepithelial cells initially span the thickness of the wall and as they continue to undergo cell division, the area of the hemispheres expands. At this early stage of development, the progenitor cells are thought to undergo primarily symmetric cell divisions and the progeny both remain in the cell cycle. Soon, however, a few cells withdraw from the cell cycle to develop as the first cortical neurons. These neurons migrate to form the preplate

Formation of cerebral cortex
Figure 8 modified from "Development of the Nervous System" 2nd Ed, Fig. 3.15.

The preplate consists of Cajal-Retzius (CR) cells and the subplate. The next step of cortical development is characterized by a large accumulation of newly post-mitotic neurons within the preplate. These neurons form the cortical plate. The cortical plate divides the preplate into the superficial marginal zone, composed primarily of the CR cells, and the intermediate zone, composed of the subplate cells and increasing numbers of incoming axons.

The developing cortex is thus described as having 4 layers (the naming of these is controversial):

  • The ventricular zone,
  • The intermediate zone,
  • The cortical plate, and
  • The marginal zone.

At the very earliest stages of cortical development, the processes of the progenitor cells span the entire thickness of the cortex. The first cortical neurons that are generated use the predominantly radial orientation of their neighboring progenitor cells, such as radial glia, to guide their migration. The accumulation of neurons within the cortical plate results in a marked increase in cortical thickness. As a result, the processes of progenitor cells are no longer able to extend to the external surface of the cortex. The cortical neurons thus migrate in a radial direction.

Then a gradual appearance of defined layers within the cortical plate is seen. The neurons that migrated from the ventricular zone move to the cortical plate and settle peripherally. Those that were generated earlier are still differentiating, thus neurons that are generated later migrate further. This results in an inside out development which is conserved in mammals. (Click here for experimental evidence)

There are two types of neurons of cerebral cortex:

  • Pyramidal shaped, glutamatergic, and
  • Stellate shaped, GABAergic inhibitory interneurons.


Subventricular zone – a secondary zone of neurogenesis

The subventricular zone is a specialized region of the anterior lateral wall of the lateral ventricle. It forms a secondary neurogenesis site later in development and is responsible for the formation of the majority of glia in the forebrain.


Morphogenesis of cortical gyri and sulci

This may depend on the different rates of cell division in a specific loci, or possibly on the relative degrees of tethering of different areas generated by the extent of their neuronal interconnections. The human brain continues to grow, even after birth, by glial proliferation, neuronal arbor enlargement and myelination of axons, but the final morphology of the brain is established early in development. The cortical gyri appear at around the 28th week of gestation and are fully developed by the first year postnatally.