Histogenesis of the cerebellum cortex
The development of the cerebellum emerges from the anterior rhombic lips, i.e., from the metencephalon (striped region in the diagram below). The cerebellum development commences in the 5th week (stages 14-16) and is completed only after birth. A detailed description of the developmental processes is to be found in chapter 22.7.
- P
- Prosencephalon
- M
- Mesencephalon
- R
- Rhombencephalon
- 1
- Cranial flexure, mesencephalic flexure
- 2
- Neck bend, cervical flexure
- 3
- Basicranial flexure, pontine flexure
The roof of the metencephalons stems from the dorsal part of the alar plate. In this region the rhombic lips arise that then push into the cavity of the IVth ventricle (striped region in the neighboring illustration). The development of the cerebellum emanates from these rhombic lips, but only toward the end of the 12th week does the cerebellum extend over the roof of the IVth ventricle.
and dorsal view (stage 23) of the brain stem
- Extraventricular rhombic lips
- Intraventricular rhombic lips
- Lower end of the rhombencephalon
- Mesencephalon
- Rostral end of the rhombencephalons
- Alar plate
- Sulcus limitans
- Basal plate
Left
Due to the increasing bending over in the region of the pontine flexure (red arrows) the rhombic lips (yellow) are forced back caudolaterally (red arrows). The alar plate moves apart in this region, the neural tube, though, remains closed at this location.
Right
Dorsal view of the brain stem of an embryo at around the 8th week. The roof of the IVth ventricle was removed. On the floor of the IVth ventricle one can distinguish the alar plate and the basal plate of the myelencephalon as well as the intraventricular and the extraventricular portions of the rhomibic lips.
In the cerebellum the gray matter is present in two forms: on the surface as cerebellum cortex and in depth as the nucleus region. Each nucleus region as an interface between the cerebellum cortex and other brain sections represents a functional unit.
On both sides of the median 4 nucleus regions can be distinguished:
- The globose nuclei and emboliform nucleus of the paleocerebellum
- The dentate nucleus, belonging to the neocerebellum
- The fastigial nucleus, ascribed to the archicerebellum
The tissue architecture of the cerebellum is very homogenous. The cerebellum cortex (cortex cerebelli) is arranged in three layers (molecular, Purkinje and granule cell layers). Afferent and efferent fibers form a regular geometric mesh.
Investigations point to the fact that the histogenesis of the cerebellum emerges from two different germinative zones. They are:
- The inner germ layer (subventricular zone) of the alar plates of the Metencephalon
- The rostral part of the rhombic lips (dorsolateral part of the alar plates) (see diagram below)
beginning of the fetal period and at the end of the 7th week post partum
- 1
- Rhombic lips (rostral, dorsolateral region of the alar plates)
- IV
- IVth ventricle
- A
- Section of a rhombic lip and ventricular zone of the alar plate
- EGL
- External granular layer
- ML
- Molecular layer
- PCL
- Purkinje cell layer
- IGL
- Inner granular layer
- WM
- White matter with dentate nucleus
- VZ
- Ventricular zone (ependyma)
The Purkinje cells, the neurons of the cerebellum nucleus as well as the stellate cells, the basket cells and the Golgi cells stem from the ventricular zone of the alar plates of the metencephalon (violet arrow). The Purkinje cells migrate along the Bergmann-radial glia into their definitive positions (PCL).
Only after the embryonic period is completed do the precursors of the granule cells leave the dorsolateral region of the rhombic lips and form the outer granular layer (EGL) at the surface of the cerebellum.
Toward the end of the fetal period the granule cells migrate in the reverse direction along the Bergmann-radial glia to the inner granular layer (blue arrow). During this migration they pass already established stellate and basket cells of the molecular layer, as well as the Purkinje cell layer. Migrating granule cells leave their axons in the molecular layer. Later, the parallel fibers arise from these cellular processes.
Those cells emerge from the inner germ layer that, following a lateral emigration from the 6th up to the 8th week, form the deep cerebellum nucleus.
At around the 9th week the neuroblasts, out of which the Purkinje cells emerge, arise in the ventricular zone. These migrate along the radial glia (Bergmann glia) to their target location. Although they are laid down early, these cells only develop their dendrites in the molecular layer between the 16th and the 28th weeks after birth. The development of the neuronal network of these cells even extends beyond it.
Each Purkinje cell creates a synaptic contact to a cerebellum core, but the axons of the Purkinje cells are the only ones that leave the cortex.
After the cerebellum core, as well as the Purkinje cells, has been formed, a third generation of neurons emerge from the ventricular layer. They are the stellate, the basket, and the Golgi cells
In contrast to these cells, the granule cells emerge form a special germinative zone that is to be found rostral and dorsolateral in the rhombic lips. After the 11th week, these cells accumulate on the cerebellum surface and there form the external germ layer. Subsequently, the granule cells leave this transient layer and migrate into the depths until they are below the Purkinje cell layer, this creating the inner granular layer in this region.
This cell migration continues for a few years following birth until the outer granular layer finally disappears.
Cerebellum in brief
- Total surface of the cerebellum cortex: 50 cm2
- Weight of the cerebellum in adults: 150 g
- Weight of the cerebellum in newborns: 21 g
- Number of Purkinje cells: 15 – 26 million