Differentiation and cell migration
The differentiation of most cell types of the future central nervous system begins from the end of the 4th week in the rhombencephalon. From that point in time, the differentiation of the neuroepithelial stem cells into neuroblasts continues spatially – cranially and caudally – just like temporally, whereby a first maximum is attained between the 15th and the 20th weeks and a second at around the 25th week. Following the neuroblasts the glioblasts are formed (whereby in this case the production maximum is reached only after birth) and finally the ependymal cells.
Over the course of their differentiation the contact of the nerve cells to the boundary membranes is lost and, at the same time, they lose their mitosis capability. The wall of the neural tube thickens and loses its epithelial character (stage 10). In parallel, the three typical cell layers of the primitive neural tube arise.
- Ventricular zone
- Intermediate layer (mantle layer)
- Marginal zone
Differentiation of the neuroblasts
Neuroblasts arise from the division of neuroepithelial stem cells. Most probably, the cells are determined during a "critical mitosis". In this, on the one hand, daughter cells are generated that keep their dividing capabilities as well as postmitotic neuroblasts that lose their connections to the boundary membrane as well as their mitosis ability irrevocably.
Indeed, the neuroblasts roll up and detach themselves from the inner boundary membrane so that a new layer, the intermediate layer (mantle layer), arises (also see "More info"). As a result, the gray substance of the CNS (stage 21) is generated from this cell layer. The immigrated neuroblasts serve as scaffold for the radial glia.
Finally, the spherical neuroblasts then develop their cell processes, the dendrites and axons. These extend into the periphery so that the third layer, the marginal zone arises. Since this layer of the neural tube contains no nerve cell bodies (perikarya), the white substance of the CNS arises from it.
This arrangement of three layers remains substantially preserved in the spinal cord but, during the further development, in the region of the cerebrum and the cerebellum, it experiences extensive changes. These restructuring processes are treated in more detail in the chapter about tissue architecture of the brain.
Differentiation of the glia cells
Although most glia cells (glioblasts) appear after neuroblasts, the radial glia cells form an exception in that already appear before neurogenesis is ended.
They play a key role in neuronal development since they represent the guiding framework for cell migration (see below). In addition, there are indications that both neurons and also glia cells can be generated from them. Thus both cell types would go bak to the same neuroepithelial predecessor cell. Investigations indicate that the neurogenetic potential of the radial glia cells varies in dependence on the narrowly confined regional cell populations of the CNS. This difference expresses itself namely in the expression of growth factors, transcription factors and in the generated cell types.
The rest of the glia cells (glioblasts) first appear in a later developmental stage and that is only after the proliferation of the neuroblasts is finished. The numerical relationship of glioblasts to neuroblasts amounts to 10 : 1. The glia cells are responsible for the sustenance of the neurons of the CNS. They also contribute to the structural stability and later form the myelin layers
Summarizing, the glia stem cells are at the origin of two cell populations:
- Out of the first population arise the cells of the radial glia cells (see above). Their cellular offshoots expand from inside out to the outer boundary membrane as Corti’s columns and serve the neuroblasts on their migration as a scaffold.
- The second population delivers a large variety of freely mobile cells. To these belong the protoplasmatic astrocytes and the fibrous astrocytes (that coat the capillaries and the neurons of the CNS) as well as the oligodendrocytes (that form the myelin sheaths in the CNS).
- In addition further cells are to be encountered that can be assigned to the microglia. These play a decisive role as phagocytes and stem from the mesenchyma. It appears they first populate the CNS with sprouting vessels.
- Toward the end of the proliferation phase the ventricular zone develops into ependyma cells that coat the ventricle system and the central canal. At those locations at which the wall of the neural tube is reduced to just this epithelial layer (lamina epithelialis), the ependyma cells differentiate themselves into cells of the plexus choroideus. The plexus choroideus epithelium forms the liquor cerebrospinalis (brain-spinal cord fluid). In addition, at certain locations, especially on the floor of the IIIrd ventricle, ependyma cells are replaced by tanycytes.
- The pituicytes (cells of the neurohypophysis) and the pinealocytes (cells of the epiphysis) are also specialized glia cells, comparable with the astrocytes.
Summary of the histogenesis of the primitive neural tube
- Ventricular zone (germinal layer):
In the ventricular zone lie the neuroepithelial stem cells out of which the neuroblasts as well as the glioblasts, the ependyma cells, the pituicytes and the pinealocytes arise. With the end of the proliferation phase the thickness of the ventricular zone is reduced and they develop into single layer ependyma
- Intermediate layer (mantle layer):
This layer consists of differentiating neuroblasts and glioblasts. They thereby form the gray matter.
- Marginal layer:
In the marginal layer are found glia cells as well as the processes (axons) of the nerve cells, thus becoming white matter.