Neural - Cerebellum Development

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Developing human cerebellum (1 month postnatal)[1]
Cerebellum structure
Mouse Purkinje neuron[2]

The cerebellum (Latin, ‘little brain’) major role is in role in sensory-motor processing that in the adult human contains half of all the brain's neurons.

Much of the basic structure of the cerebellum comes the historic histological studies and staining of Ramón Cahal (1852 - 1934) and Camillo Golgi (1843 - 1926).

Cerebellum History
Santiago Ramon y Cahal in laboratory.jpg
Santiago Ramon y Cahal (1852 - 1934) a Spanish researcher used then new histology Golgi staining techniques to identify the cerebellum cellular structure.

His work was a turning point in our understanding of the structure of the brain, that until then had been described as a "syncytium" and not consisting of discrete cellular elements.

For this research and other work on defining the structure of the brain he, along with Camillo Golgi (1843 - 1926), received the 1906 Nobel Prize in Medicine.

Camillo Golgi.jpg
Camillo Golgi (1843 - 1926) developed the histology silver staining technique, though is best known today for the cellular organelle that bears his name, the Golgi apparatus.

History - Embryologists


Transverse section of a cerebellar folium.

Neural development is one of the earliest systems to begin and the last to be completed after birth. This development generates the most complex structure within the embryo and the long time period of development means in utero insult during pregnancy may have consequences to development of the nervous system.

"For every neuron added to the cerebral cortex in evolution, four neurons are added to the cerebellum."[3]

The adult cerebellum anatomy consists of three parts, the vermis (median) and the two hemispheres (lateral), which are continuous with each other.

Within the neural tube stem cells generate the 2 major classes of cells that make the majority of the nervous system : neurons and glia. Both these classes of cells differentiate into many different types generated with highly specialized functions and shapes. This section covers the establishment of neural populations, the inductive influences of surrounding tissues and the sequential generation of neurons establishing the layered structure seen in the brain and spinal cord.

  • Neural development beginnings quite early, therefore also look at notes covering Week 3- neural tube and Week 4-early nervous system.
  • Development of the neural crest and sensory systems (hearing/vision/smell) are only introduced in these notes and are covered in other notes sections.

Neural Links: ectoderm | neural | neural crest | ventricular | sensory | Stage 22 | gliogenesis | neural fetal | Medicine Lecture - Neural | Lecture - Ectoderm | Lecture - Neural Crest | Lab - Early Neural | neural abnormalities | folic acid | iodine deficiency | Fetal Alcohol Syndrome | neural postnatal | neural examination | Histology | Historic Neural | Category:Neural
Neural Parts: neural | prosencephalon | telencephalon cerebrum | amygdala | hippocampus | basal ganglia | diencephalon | epithalamus | thalamus | hypothalamus‎ | pituitary | pineal | mesencephalon | tectum | rhombencephalon | metencephalon | pons | cerebellum | myelencephalon | medulla oblongata | spinal cord | neural vascular | ventricular | lateral ventricles | third ventricle | cerebral aqueduct | fourth ventricle | central canal | meninges | Category:Ventricular System | Category:Neural

Some Recent Findings

  • Calm1 signaling pathway is essential for the migration of mouse precerebellar neurons.[4] "Calmodulin (CaM is encoded by three non-allelic CaM (Calm) genes (Calm1, Calm2 and Calm3), which produce an identical protein with no amino acid substitutions. We found that these CaM genes are expressed in migrating PCNs. When the expression of CaM from this multigene family was inhibited by RNAi-mediated acute knockdown, inhibition of Calm1 but not the other two genes caused defective PCN migration. Many PCNs treated with Calm1 shRNA failed to complete their circumferential tangential migration and thus failed to reach their prospective target position. Those that did reach the target position failed to invade the depth of the hindbrain through the required radial migration. Overall, our results suggest the participation of CaM in both the tangential and radial migration of PCNs."
  • Abnormal cerebellar development and Purkinje cell defects in Lgl1-Pax2 conditional knockout mice[5] "Lgl1 was initially identified as a tumour suppressor in flies and is characterised as a key regulator of epithelial polarity and asymmetric cell division. ...Consistent with this abnormal behaviour, homozygous mice possessed a smaller cerebellum with fewer lobes, reduced granule precursor cell (GPC) proliferation, decreased Purkinje cell (PC) quantity and dendritic dysplasia. Loss of Lgl1 in the cerebellum led to hyperproliferation and impaired differentiation of neural progenitors in ventricular zone."
  • Ectopic cerebellar cell migration causes maldevelopment of Purkinje cells and abnormal motor behaviour in Cxcr4 null mice.[6] "SDF-1/CXCR4 signalling plays an important role in neuronal cell migration and brain development. ...Together, these results suggest ectopic the migration of granule cells impairs development of Purkinje cells, causes gross cerebellar anatomical disruption and leads to behavioural motor defects in Cxcr4 null mice."
  • Preterm delivery disrupts the developmental program of the cerebellum[1] "A rapid growth in human cerebellar development occurs in the third trimester, which is impeded by preterm delivery. ...We report that premature birth and development in an ex-utero environment leads to a significant decrease in the thickness and an increase in the packing density of the cells within the external granular layer and the inner granular layer well, as a reduction in the density of bergmann glial fibres. In addition, this also leads to a reduced expression of sonic hedgehog in the purkinje layer. We conclude that the developmental program of the cerebellum is specifically modified by events that follow preterm delivery."
  • Ontogeny-recapitulating generation and tissue integration of ES cell-derived Purkinje cells [7] "Purkinje cells are the sole output neurons of the cerebellar cortex and their dysfunction causes severe ataxia. We found that Purkinje cells could be robustly generated from mouse embryonic stem (ES) cells by recapitulating the self-inductive signaling microenvironments of the isthmic organizer."
More recent papers
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Search term: Cerebellum Embryology

<pubmed limit=5>Cerebellum Embryology</pubmed>

Development Overview

Neuralation begins at the trilaminar embryo with formation of the notochord and somites, both of which underly the ectoderm and do not contribute to the nervous system, but are involved with patterning its initial formation. The central portion of the ectoderm then forms the neural plate that folds to form the neural tube, that will eventually form the entire central nervous system.

Early developmental sequence: Epiblast - Ectoderm - Neural Plate - Neural groove and Neural Crest - Neural Tube and Neural Crest
Neural Tube Development
Neural Tube Primary Vesicles Secondary Vesicles Adult Structures
week 3 week 4 week 5 adult
neural plate
neural groove
neural tube

prosencephalon (forebrain) telencephalon Rhinencephalon, Amygdala, hippocampus, cerebrum (cortex), hypothalamus‎, pituitary | Basal Ganglia, lateral ventricles
diencephalon epithalamus, thalamus, Subthalamus, pineal, posterior commissure, pretectum, third ventricle
mesencephalon (midbrain) mesencephalon tectum, Cerebral peduncle, cerebral aqueduct, pons
rhombencephalon (hindbrain) metencephalon cerebellum
myelencephalon medulla oblongata, isthmus
spinal cord, pyramidal decussation, central canal
Human embryo neural groove (Carnegie stage 10)
Neural groove closing to neural tube, early week 4
(Stage 10)

The following text description is from a study of 20 human embryos and fetuses between 6 weeks to 16 weeks from the Madrid Collection.[8]

  • 6 weeks (CRL 12–16 mm) - anlage of the cerebellum was first identified as a pair of thickenings on the lateral site of the alar plate that faced the fourth ventricle.
  • 7-9 weeks (CRL 28 mm) - rhombic lip (a pair of thickenings of the alar plate) protruded dorsally, bent laterally, extended ventrolaterally and fused with the medially located midbrain. During that process, the primitive choroid plexus appeared to become involved in the cerebellar hemisphere to form a centrally located eosinophilic matrix. At that stage, the inferior olive had already developed in the thick medulla. Thus, the term 'bulbo-pontine extension' may represent an erroneous labeling of a caudal part of the rhombic lip. The cerebellar vermis developed much later than the hemisphere possibly from a midline dark cell cluster near the aqueduct.
  • 11–12 weeks (CRL 70–90 mm) - cerebellar hemisphere became as thick as the mid- brain. In the hemisphere, a laminar configuration became evident but the central eosinophilic matrix remained pres- ent. Fissures of the future vermis appeared in the midline area (Fig. 6): the developing fissures provided island-like structures in horizontal sections. The hemisphere and ver- mis, including the surfaces of the fissures, were covered by the external germinal cell layer.
  • 15–16 weeks (CRL 110–130 mm) - cerebellar hemisphere contained the primitive dentate nucleus. The nodule and flocculus were identified, vermis became as thick as the hemisphere and it accompanied several deep fissures.

Cerebellar Cells

These drawings of cerebellar cells were based upon electron micrograph images from the rat cerebellum.[9]

Gray, Henry. Anatomy of the Human Body. Philadelphia: Lea & Febiger, 1918.

Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. The Cerebellum


Foliation Defects

Mouse cerebellar foliation defects.jpg

Mouse Cerebellar Foliation Defects[10]

(A–B) Midsagittal sections of newborn (P0) wild-type and Mdm2puro/Δ7-9 cerebella stained with H&E. (C–D) Superimposition of P0 (purple outline), P7 (blue outline), and adult (green outline) cerebella from wild-type (C) or Mdm2puro/Δ7-9 (D) mice. By P7, all four primary fissures, as well as two additional fissures, are evident in Mdm2puro/Δ7-9 mice. Moreover, even in adulthood, the mutant cerebellum does not reach the size or complexity of the wild-type cerebellum. Abbreviations are: prc, precentral; pc, pre-culminate; pr, primary; pp, prepyramidal; sec, secondary; pl, posterolateral fissures.

Pontocerebellar Hypoplasia

Pontocerebellar Hypoplasia (MRI)[11]

Pontocerebellar Hypoplasia (PCH) are very rare, inherited progressive neurodegenerative disorders with prenatal onset (for recent review see[11]). The major features are: hypoplasia or atrophy of cerebellum and pons, progressive microcephaly, and variable cerebral involvement. There is a further classification of 7 different subtypes (PCH1-7) and there is prenatal testing for the related inherited mutations.

  • PCH2, PCH4, PCH5 - Mutations in the 3 tRNA splicing endonuclease subunit genes.
  • PCH6 - Mutations in the nuclear encoded mitochondrial arginyl- tRNA synthetase gene.
  • PCH1 - Mutations in the tRNA splicing endonuclease, the mitochondrial arginyl- tRNA synthetase and the vaccinia related kinase1.


Medulloblastomas are the most common childhood primary central nervous system tumour. They are thought to arise in the developing cerebellum from the precursors of the granule cell.


  1. 1.0 1.1 <pubmed>21858122</pubmed>| PLoS One
  2. <pubmed>11724815</pubmed>| PMC2150878 | J Cell Biol.
  3. <pubmed>20300467</pubmed>| Front Neuroanat.
  4. <pubmed>25519244</pubmed>
  5. <pubmed>25050931</pubmed>
  6. <pubmed>24516532</pubmed>
  7. <pubmed>20835252</pubmed>
  8. <pubmed>21380713</pubmed>
  9. <pubmed>14222815</pubmed>| PMC2106521 | J Cell Biol.
  10. <pubmed>21437245</pubmed>| PLoS One.
  11. 11.0 11.1 <pubmed>21749694</pubmed>| Orphanet J Rare Dis.



<pubmed></pubmed> <pubmed>25336734</pubmed> <pubmed>22396330</pubmed>| PMC3359460 <pubmed>21295689</pubmed> <pubmed>19732611</pubmed> <pubmed>17408845</pubmed> <pubmed>16243598</pubmed> <pubmed>15610138</pubmed> <pubmed>12843872</pubmed>


<pubmed></pubmed> <pubmed></pubmed> <pubmed>21380713</pubmed> <pubmed>20460306</pubmed> <pubmed>15496441</pubmed>

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Search Pubmed: Cerebellum Embryology | Cerebellum Development | Medulloblastoma


  • Bergmann glia - a cerebellar radial glial population that in development act as scaffolds for the radial migration of granule cell precursors from the external germinal layer (EGL or outer granular layer) to the inner granular cell layer (IGL).
  • cerebellar nuclei - clusters of glutamatergic and GABAergic neurons located in the cerebellar white matter that are the synaptic targets of the majority of Purkinje cells. Projection neurons within nuclei account for the output of the cerebellum. Cerebellar nuclei are often termed ‘deep’ although the designation is superfluous.
  • External Germinal Layer - (EGL or outer granular layer) a developmental transient layer that is lost following granule cell migration.
  • Granule cell - neurons in the internal granule layer that receive excitatory inputs from mossy fibres, that originate in the pons, medulla and spinal cord. These glutamatergic excitatory neutrons receive local inhibitory inputs from Golgi neurons. Granule cells axons are T-shaped and extend into the molecular layer synapsing on Purkinje cell dendrites.
  • Inner Granular Layer - (IGL) granule neurons (granule cell) lies deep to the Purkinje cell layer.
  • Purkinje cell - neurons located in the cerebellar cortex that receive excitatory inputs from granule cell parallel fibres and inhibitory input from climbing fibres of the inferior olive. These GABAergic inhibitory neurons axons mainly extend to the deep cerebellar nuclei, some axons also directly innervate hindbrain vestibular targets.


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Cite this page: Hill, M.A. (2020, October 28) Embryology Neural - Cerebellum Development. Retrieved from

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© Dr Mark Hill 2020, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G