Neurosurgery notes/Anatomy/Embryology/6 stages of CNS maturation/Cerebellum

Cerebellum

View Details
Status
Done
logo
Parent item
6 stages of CNS maturation

General

  • A process that starts 30 days post-conception → until 2 years of postnatal age
    • exponential proliferation of the granule cell progenitors (GCP) starts at 24th gestational week and continues during postnatal age, achieving a peak at the 32nd gestational week
      • This process provokes an increase in the cerebellar mass that exceeds the volume of the posterior fossa, determining a series of folding along the anterior/posterior axis and allowing the expansion of the cerebellar surface
      • This foliation starts with the organization of the “anchoring centers” and the appearance of scissures that form the folia and separate the lobes.
  • Cerebellum originates from the dorsal portion of the hindbrain

4 steps of cerebellum development:

  1. Organization of the cerebellar territory
      • In the upper part of the hindbrain, the rhombomere 1
        • The expression of the basic-helix-loop-helix proteins ATOH1 marks the upper rhombic lip (RL)
        • The expression of the basic-helix-loop-helix proteins PTF1a marks the ventricular zone (VZ)
      • In the lower portion of the hindbrain (lower RL)
        • Forms
          • Roof plate
            • A transient pseudostratified epithelium constituted by a population of cells expressing the protein WNT1
            • This layer covers the fourth ventricle roof
          • Choroid plexus cells
            • Production of the cerebrospinal fluid (CSF)
  1. Establishment of cerebellar progenitors (GABAergic and glutamatergic ones)
      • Cerebellar nuclei cells are the first to be born
          • GABAergic ones descending from the VZ
          • Ventricular zone: Alar plate
          • The ventricular zone is the neuroepithelium of the alar plate which later develops into the roof of the fourth ventricle.
          • Becoming interneurons
          • Derives
            • Neurons
              • Purkinje cells
                • Two groups of PCs leave the VZ to form the so-called “Purkinje cell plate”
                  • Early PCs
                    • born in the posterior VZ
                    • migrate tangentially, then change orientation toward the EGL under the influence of the protein reelin secreted by the GCPs
                  • Late PCs
                    • born in the anterior VZ
                    • move following a radial pattern, guided by Bergmann glial fibres signalling
                • Subsequently, the PCs plate reorganizes itself to form a monolayer of PCs, beneath which the IGL will locate
                • The granule cells produce trophic factors necessary to develop the PCs dendritic trees.
                • At 20th gestational week, the human cerebellum presents a transient cellular region called “lamina dissecans,” between the PCs layer and the IGL.
                  • Its function in the cerebellar development is yet unknown and it disappears by the 32nd gestational week
              • Interneurons
                • All inhibitory interneurons come from a common progenitor expressing a protein called PAX2 and,
                • During the 3rd trimester of pregnancy
                  • differentiate into
                    • Golgi cells, that will establish in the granule layer
                    • Stellate and basket cells, that will take place in the molecular layer
            • Glial cells
              • Originate from the VZ
              • Eg
                • Cerebellar astrocytes
                • Bergmann glia (BG)
                • A small number of oligodendrocytes expressing Olig2 domain
              • Glial cells are involved in numerous processes of the cerebellar development:
                • cellular migration (especially the PCs)
                • synapse organization
                • production of neurotrophic factors
                • formation of the blood-brain barrier
          • Neurotransmitter: inhibitory GABAergic
          Glutamatergic ones originating from the RL
          • Rhomboid lip: Neural folds
          • Derives
            • Cerebellar nuclei neurons
            • Interneurons
              • Unipolar brush cells
                • Especially represented in the flocculonodular lobe
            • Granule layer cells
              • are the glutamatergic neurons
              • spring up from granule cell progenitors (GCP)
              • migrates tangentially to form the external granule layer (EGL)
                • following FGF8 and SHH signalling,
                • goes through clonal expansion during the late pregnancy period,
                • determining the formation of a six-eight cells layer
                • This process produces an amount of granule neurons so large that it overcomes the cerebral cortex ones
              • Later, GCPs differentiate and move inward into the cerebellar anlage to form the internal granule layer (IGL).
              • During the postnatal age, the RL continues to produce granule cells and the EGL progressively disappears during the second year
      • Development of the cerebellar nuclei starts with a “nuclear transitory zone” in a marginal position.
        • The glutamatergic neurons follow a tangential pattern of migration and establish the GABAergic interneurons further maturation.
          • The lateral nuclei develop early and project to thalamus and midbrain,
          • The medial group appears later and make connections to the hindbrain
        • Derivatives of the hindbrain that will form extra-cerebellar structures of the CNS also arise from the RL, like the pontine nuclei. A strict interconnection occurs between brainstem nuclei and cerebellum as the brainstem delivers proprioceptive/vestibular/auditory sensations and cortical information to the cerebellum
  1. Migration of the granule cells
  1. Formation of the cerebellar nuclei and circuitry
notion image
notion image