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

Cerebellum

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6 stages of CNS maturation
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May 31, 2026 01:08 AM GMT+0

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)
  2. 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
  3. Migration of the granule cells
  4. Formation of the cerebellar nuclei and circuitry
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