Neural - Cerebellum Development

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Introduction

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

See also the early descriptive study by Palmgren (1921 )[3]

Gray0706.jpg

Transverse section of a cerebellar folium.

See also the description by Myers BD. A study of the development of certain features of the cerebellum. (1920) Carnegie Instn. Wash. Publ., Contrib. Embryol., 41:

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."[4]


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

Some Recent Findings

  • Bergmann glial Sonic hedgehog signaling activity is required for proper cerebellar cortical expansion and architecture[5] "Neuronal-glial relationships play a critical role in the maintenance of central nervous system architecture and neuronal specification. A deeper understanding of these relationships can elucidate cellular cross-talk capable of sustaining proper development of neural tissues. In the cerebellum, cerebellar granule neuron precursors (CGNPs) proliferate in response to Purkinje neuron-derived Sonic hedgehog (Shh) before ultimately exiting the cell cycle and migrating radially along Bergmann glial fibers. However, the function of Bergmann glia in CGNP proliferation remains not well defined. Interestingly, the Hh pathway is also activated in Bergmann glia, but the role of Shh signaling in these cells is unknown. In this study, we show that specific ablation of Shh signaling using the tamoxifen-inducible TNCYFP-CreER line to eliminate Shh pathway activator Smoothened in Bergmann glia is sufficient to cause severe cerebellar hypoplasia and a significant reduction in CGNP proliferation. TNCYFP-CreER; SmoF/- (SmoCKO) mice demonstrate an obvious reduction in cerebellar size within two days of ablation of Shh signaling. Mutant cerebella have severely reduced proliferation and increased differentiation of CGNPs due to a significant decrease in Shh activity and concomitant activation of Wnt signaling in SmoCKO CGNPs, suggesting that this pathway is involved in cross-talk with the Shh pathway in regulating CGNP proliferation. In addition, Purkinje cells are ectopically located, their dendrites stunted, and the Bergmann glial network disorganized. Collectively, these data demonstrate a previously unappreciated role for Bergmann glial Shh signaling activity in the proliferation of CGNPs and proper maintenance of cerebellar architecture." SHH
  • The modular architecture and neurochemical patterns in the cerebellar cortex[6] "The review deals with topical issues of the neuronal arrangement underlying basic cerebellar functions. The cerebellum and its auxiliary structures contain several hundreds of modules (so called "microzones"). Each module receives the corticopetal input specific for the lobule it belongs to and forms the topographic projection. The precision of the major input-output signal flow in the cerebellar cortex is provided by a pronounced stratification of its synaptic zones of a various origin and regular topography of its afferent connections, interneurons, and efferent neurons. There is a nice match between the anatomical and functional coordinates of the modules, whose spatial boundaries are determined by the spread of afferent excitation and local interneuron connections. The dynamic characteristics of the modules are analyzed by the example of the formation of the nitrergic neuron ensembles and cerebellar projections of corticopetal fibers. The authors discuss the cerebellar blood flow and its relation to the activity of NO/GABAergic Lugaro cells and other interneurons in the cerebellar cortex."
  • Pre- and Postnatal Neuroimaging of Congenital Cerebellar Abnormalities[7] "The human cerebellum has a protracted development that makes it vulnerable to a broad spectrum of developmental disorders including malformations and disruptions. Starting from 19 to 20 weeks of gestation, prenatal magnetic resonance imaging (MRI) can reliably study the developing cerebellum. Pre- and postnatal neuroimaging plays a key role in the diagnostic work-up of congenital cerebellar abnormalities. Diagnostic criteria for cerebellar malformations and disruptions are based mostly on neuroimaging findings. The diagnosis of a Dandy-Walker malformation is based on the presence of hypoplasia, elevation, and counterclockwise upward rotation of the cerebellar vermis and cystic dilatation of the fourth ventricle, which extends posteriorly filling out the posterior fossa. For the diagnosis of Joubert syndrome, the presence of the molar tooth sign (thickened, elongated, and horizontally orientated superior cerebellar peduncles and an abnormally deep interpeduncular fossa) is needed. The diagnostic criteria of rhombencephalosynapsis include a complete or partial absence of the cerebellar vermis and continuity of the cerebellar hemispheres across the midline. Unilateral cerebellar hypoplasia is defined by the complete aplasia or hypoplasia of one cerebellar hemisphere." MRI
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Cerebellum Embryology

R A Imam, H N Gadallah Acrylamide adverse cerebellar changes in rats: possible oligodendrogenic role of omega 3 and green tea. Folia Morphol. (Warsz): 2018; PubMed 30402879

Basma Emad Aboulhoda, Sherif S Hassan Effect of prenatal tramadol on postnatal cerebellar development: Role of oxidative stress. J. Chem. Neuroanat.: 2018; PubMed 30342117

Peng-Peng Jin, Feng Xia, Bin-Fang Ma, Zhen Li, Guo-Feng Zhang, Yan-Chun Deng, Zhi-Lan Tu, Xing-Xing Zhang, Shuang-Xing Hou Spatiotemporal expression of NDRG2 in the human fetal brain. Ann. Anat.: 2018; PubMed 30312765

Patrick Piero Bovio, Henriette Franz, Stefanie Heidrich, Tudor Rauleac, Fabian Kilpert, Thomas Manke, Tanja Vogel Differential Methylation of H3K79 Reveals DOT1L Target Genes and Function in the Cerebellum In Vivo. Mol. Neurobiol.: 2018; PubMed 30302725

Stéphane Zaffran, Gaëlle Odelin, Sonia Stefanovic, Fabienne Lescroart, Heather C Etchevers Ectopic expression of Hoxb1 induces cardiac and craniofacial malformations. Genesis: 2018, 56(6-7);e23221 PubMed 30134070

Older papers  
  • Calm1 signaling pathway is essential for the migration of mouse precerebellar neurons.[8] "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[9] "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.[10] "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[11] "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."

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 Primary Vesicles Secondary Vesicles Adult Structures
week 3 week 4 week 5 adult
neural plate
neural groove
neural tube

Brain
Prosencephalon Telencephalon Rhinencephalon, Amygdala, Hippocampus, Cerebrum (Cortex), Hypothalamus, Pituitary | Basal Ganglia, lateral ventricles
Diencephalon Epithalamus, Thalamus, Subthalamus, Pineal, third ventricle
Mesencephalon Mesencephalon Tectum, Cerebral peduncle, Pretectum, cerebral aqueduct
Rhombencephalon Metencephalon Pons, Cerebellum
Myelencephalon Medulla Oblongata
Spinal Cord
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.[12]

  • 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.

Early Brain Vesicles

Primary Vesicles Secondary Vesicles
CNS primary vesicles.jpg CNS secondary vesicles.jpg
week 3 to 4 week 5 +

Embryonic Cerebellum

Week 4

Human Stage13 sagittal upper half02.jpg This midline section through the upper half of the embryo shows the 3 primary vesicle regions (unlabeled image).

The cerebellum will develop from the hindbrain (rhombencephalon) region.

Adjacent to the forth ventricle (see as the enlarged dark dorsal region).


Human Embryo (Carnegie stage 13) 28 - 32 days.

Week 8

Carnegie stage 21
Human Stage21 neural01.jpg Human Stage21 neural02.jpg
lateral view (scale bar 1 mm) Median view

Fetal Cerebellum

Week 10

Human- fetal week 10 cerebellum A.jpg Human- fetal week 10 cerebellum B.jpg
Plane A (midline) Plane B (medial)
Human- fetal week 10 cerebellum C.jpg Human- fetal week 10 cerebellum D.jpg
Plane C (lateral) Plane D (most lateral)


Links: 10 week Fetal | Fetal Development

Third Trimester

Developing human cerebellum 01.jpg

Developing human cerebellum preterm[1]

A greater EGL cell density and reduced EGL thickness were reported in preterms with ex-utero exposure, as compared to their age matched stillborn controls.

Cerebellar Cells

These drawings of cerebellar cells were based upon electron micrograph images from the rat cerebellum.[13]


Historic Description

Gray H. Anatomy of the human body. (1918) Philadelphia: Lea & Febiger.

"The cerebellum is developed in the roof of the anterior part of the hind-brain (Figs. 649 to 654). The alar laminæ of this region become thickened to form two lateral plates which soon fuse in the middle line and produce a thick lamina which roofs in the upper part of the cavity of the hind-brain vesicle; this constitutes the rudiment of the cerebellum, the outer surface of which is originally smooth and convex. The fissures of the cerebellum appear first in the vermis and floccular region, and traces of them are found during the third month; the fissures on the cerebellar hemispheres do not appear until the fifth month. The primitive fissures are not developed in the order of their relative size in the adult—thus the horizontal sulcus in the fifth month is merely a shallow groove. The best marked of the early fissures are: (a) the fissura prima between the developing culmen and declive, and (b) the fissura secunda between the future pyramid and uvula. The flocculus and nodule are developed from the rhombic lip, and are therefore recognizable as separate portions before any of the other cerebellar lobules. The groove produced by the bending over of the rhombic lip is here known as the floccular fissure; when the two lateral walls fuse, the right and left floccular fissures join in the middle line and their central part becomes the post-nodular fissure."
Transverse section of a cerebellar folium. (Cajal)

Researcher timeline based on a recent review on cerebellum[14]

  • Rolando - role in movement control
  • Flourens - role in movement coordination
  • Purkinje (1837) - histology of the cerebellar cortex
  • Luciani (1891) - cerebellum has a tonic facilitating effect on central structures
  • Bolk (1906) - localization for coordinating action on the motor system (medio-lateral organization)
  • Cajal - histology of cortex circuitry
  • Eccles and Ito - inhibitory interneurons and the Purkinje cells, excitatory connections of mossy and climbing afferents and granule cells
  • Babinski and Holmes - anatomoclinical insights
  • Marr and Albus - theories involving cognition and emotion
  • Leiners and Dow
  • Magnus - cerebellum no role in body posture

Precerebellar Neurons

Precerebellar neurons (PCNs) are born in the hindbrain alar plate in the specific region called the rhombic lip (for review see[15]). From there they migrate by a process termed nucleokinesis[16], extending a cytoplasmic process then move their nucleus.


In recent years a number of different chemotactic positive and negative factors have been suggested to have a role in driving the guided migration of these cells. Many signals are thought to be mediated through the Rho family GTPases links to the cytoskeleton.

  • netrin-1[17]
  • Slit
  • Nr-CAM
  • Calm1 signaling pathway[8]

Cerebellar Nuclei

Cerebellar Nuclei
Nucleus/Nuclei
Location
Function
Fastigial Nucleus
Most medially located of the cerebellar nuclei. Receives input from the vermis and cerebellar afferents that carry vestibular, proximal somatosensory, auditory and visual information.
Interposed Nuclei
Consists of emboliform nucleus and globose nucleus. Interposed nuclei are situated laterally with respect to the fastigial nucleus. Receives input from intermediate zone and cerebellar afferents that carry spinal, proximal somatosensory, auditory and visual information.
Dentate Nucleus
Largest of the cerebellar nuclei. Lateral to interposed nuclei. Receives input from lateral hemisphere and cerebellar afferents that carry information from cerebral cortex.
Vestibular Nuclei
Located outside cerebellum in the medulla. Considered to be cerebellar nuclei as their connectivity patterns are identical to those of cerebellar nuclei. Receive input from flocculonodular lobe and from the vestibular labyrinth.
Links: cerebellum

Cerebellar Pathways

Mouse cerebellum connections 01.jpg (A) Regions that send input to the cerebellum.



Abbreviations: AMG, amygdala; BG, basal ganglia; ECN, external cuneate nucleus; HIP, hippocampus; HYP; hypothalamus; IO, inferior olive; LC, locus coeruleus; PAG, periaqueductal gray; PN, pontine nuclei; RET, reticular nucleus; RN, red nucleus; SC, spinal cord; SUP, superior colliculi; TH, thalamus; VN, vestibular nuclei.




(B) Regions that receive information from the cerebellum. Note that the TH is a major relay station for cerebellar input to the cortex while the PN is the primary gateway for cerebral cortical input to the cerebellum.


Cerebellum connections to the brain and spinal cord (mouse).[18]

Abnormalities

Dandy-Walker Syndrome

Dandy-Walker Syndrome/Malformation (DWS) is a cerebellar hypoplasia and upward rotation of the cerebellar vermis with ventricular enlargement (cystic dilation of the fourth ventricle). Named in 1954 after the earlier identification by Walter Dandy (1914) and Arthur Earl Walker (1942), two USA neurosurgeons.

Walter Dandy (1886 – 1946) Arthur Earl Walker (1907 – 1995).

International Classification of Diseases Q03 Congenital hydrocephalus Incl.: hydrocephalus in newborn Excl.: Arnold-Chiari syndrome (Q07.0) hydrocephalus: acquired (G91.-) due to congenital toxoplasmosis (P37.1) with spina bifida (Q05.0-Q05.4)

  • Q03.0 Malformations of aqueduct of Sylvius Aqueduct of Sylvius: anomaly obstruction, congenital stenosis
  • Q03.1 Atresia of foramina of Magendie and Luschka Dandy-Walker syndrome
Links: MP4 movie | Neural Abnormalities | Cerebellum Development | Ultrasound | OMIM - Dandy-Walker Syndrome | Movies
US Dandy-Walker 01.jpg
 ‎‎Dandy-Walker
Page | Play


Foliation Defects

Mouse cerebellar foliation defects.jpg

Mouse Cerebellar Foliation Defects[19]

(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.

Joubert Syndrome

Joubert syndrome (Joubert-Boltshauser syndrome, Cerebelloparenchymal disorder 4, Cerebellar vermis agenesis) is a rare disease of the cerebellum. Identified as a ciliopathy, characterized by the absence or underdevelopment of the cerebellar vermis, that controls balance and coordination. There is also malformation of the stem, connecting the brain and spinal cord. A recent super-resolution microscopy study has shown that the syndrome is caused by disruption of the ciliary transition-zone architecture. [20] Ciliopathies are a class of cell abnormalities that can be caused by mutations in components of the cellular transition zone, a domain near the base of the cilium, that controls the protein composition of its membrane.

  • hypotonia - weak muscle tone
  • ataxia - difficulty coordinating movements
  • hyperpnea - episodes of fast breathing (improves with age and usually disappears around 6 months of age)
  • oculomotor apraxia - difficulty moving the eyes from side to side.
  • language and motor skills
  • mild to severe intellectual disability
  • distinctive facial features - broad forehead, arched eyebrows, droopy eyelids (ptosis), widely spaced eyes, low-set ears, and a triangular-shaped mouth.


Links: NIH - Rare Diseases

Pontocerebellar Hypoplasia

Pontocerebellar Hypoplasia (MRI)[21]

Pontocerebellar Hypoplasia (PCH) are very rare, inherited progressive neurodegenerative disorders with prenatal onset (for recent review see[22]). 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.

Medulloblastoma

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.

References

  1. 1.0 1.1 1.2 Haldipur P, Bharti U, Alberti C, Sarkar C, Gulati G, Iyengar S, Gressens P & Mani S. (2011). Preterm delivery disrupts the developmental program of the cerebellum. PLoS ONE , 6, e23449. PMID: 21858122 DOI.
  2. Priller J, Persons DA, Klett FF, Kempermann G, Kreutzberg GW & Dirnagl U. (2001). Neogenesis of cerebellar Purkinje neurons from gene-marked bone marrow cells in vivo. J. Cell Biol. , 155, 733-8. PMID: 11724815 DOI.
  3. Palmgren A. Embryological and morphological studies on the mid-brain and cerebellum of vertebrates. (1921) Acta Zoologica. 64(5): 2-94.
  4. Herculano-Houzel S. (2010). Coordinated scaling of cortical and cerebellar numbers of neurons. Front Neuroanat , 4, 12. PMID: 20300467 DOI.
  5. Cheng FY, Fleming JT & Chiang C. (2018). Bergmann glial Sonic hedgehog signaling activity is required for proper cerebellar cortical expansion and architecture. Dev. Biol. , 440, 152-166. PMID: 29792854 DOI.
  6. Kalinichenko SG & Pushchin II. (2018). The modular architecture and neurochemical patterns in the cerebellar cortex. J. Chem. Neuroanat. , 92, 16-24. PMID: 29753860 DOI.
  7. Poretti A, Boltshauser E & Huisman TA. (2016). Pre- and Postnatal Neuroimaging of Congenital Cerebellar Abnormalities. Cerebellum , 15, 5-9. PMID: 26166429 DOI.
  8. 8.0 8.1 Kobayashi H, Saragai S, Naito A, Ichio K, Kawauchi D & Murakami F. (2015). Calm1 signaling pathway is essential for the migration of mouse precerebellar neurons. Development , 142, 375-84. PMID: 25519244 DOI.
  9. Hou C, Ding L, Zhang J, Jin Y, Sun C, Li Z, Sun X, Zhang T, Zhang A, Li H & Gao J. (2014). Abnormal cerebellar development and Purkinje cell defects in Lgl1-Pax2 conditional knockout mice. Dev. Biol. , 395, 167-81. PMID: 25050931 DOI.
  10. Huang GJ, Edwards A, Tsai CY, Lee YS, Peng L, Era T, Hirabayashi Y, Tsai CY, Nishikawa S, Iwakura Y, Chen SJ & Flint J. (2014). Ectopic cerebellar cell migration causes maldevelopment of Purkinje cells and abnormal motor behaviour in Cxcr4 null mice. PLoS ONE , 9, e86471. PMID: 24516532 DOI.
  11. Muguruma K, Nishiyama A, Ono Y, Miyawaki H, Mizuhara E, Hori S, Kakizuka A, Obata K, Yanagawa Y, Hirano T & Sasai Y. (2010). Ontogeny-recapitulating generation and tissue integration of ES cell-derived Purkinje cells. Nat. Neurosci. , 13, 1171-80. PMID: 20835252 DOI.
  12. Cho KH, Rodríguez-Vázquez JF, Kim JH, Abe H, Murakami G & Cho BH. (2011). Early fetal development of the human cerebellum. Surg Radiol Anat , 33, 523-30. PMID: 21380713 DOI.
  13. HERNDON RM. (1964). THE FINE STRUCTURE OF THE RAT CEREBELLUM. II. THE STELLATE NEURONS, GRANULE CELLS, AND GLIA. J. Cell Biol. , 23, 277-93. PMID: 14222815
  14. Voogd J & Koehler PJ. (2018). Historic notes on anatomic, physiologic, and clinical research on the cerebellum. Handb Clin Neurol , 154, 3-26. PMID: 29903448 DOI.
  15. Bloch-Gallego E, Causeret F, Ezan F, Backer S & Hidalgo-Sánchez M. (2005). Development of precerebellar nuclei: instructive factors and intracellular mediators in neuronal migration, survival and axon pathfinding. Brain Res. Brain Res. Rev. , 49, 253-66. PMID: 16111554 DOI.
  16. Tsai LH & Gleeson JG. (2005). Nucleokinesis in neuronal migration. Neuron , 46, 383-8. PMID: 15882636 DOI.
  17. Killeen MT & Sybingco SS. (2008). Netrin, Slit and Wnt receptors allow axons to choose the axis of migration. Dev. Biol. , 323, 143-51. PMID: 18801355 DOI.
  18. Reeber SL, Otis TS & Sillitoe RV. (2013). New roles for the cerebellum in health and disease. Front Syst Neurosci , 7, 83. PMID: 24294192 DOI.
  19. Malek R, Matta J, Taylor N, Perry ME & Mendrysa SM. (2011). The p53 inhibitor MDM2 facilitates Sonic Hedgehog-mediated tumorigenesis and influences cerebellar foliation. PLoS ONE , 6, e17884. PMID: 21437245 DOI.
  20. Shi X, Garcia G, Van De Weghe JC, McGorty R, Pazour GJ, Doherty D, Huang B & Reiter JF. (2017). Super-resolution microscopy reveals that disruption of ciliary transition-zone architecture causes Joubert syndrome. Nat. Cell Biol. , 19, 1178-1188. PMID: 28846093 DOI.
  21. Namavar Y, Barth PG, Poll-The BT & Baas F. (2011). Classification, diagnosis and potential mechanisms in pontocerebellar hypoplasia. Orphanet J Rare Dis , 6, 50. PMID: 21749694 DOI.
  22. Namavar Y, Barth PG, Poll-The BT & Baas F. (2011). Classification, diagnosis and potential mechanisms in pontocerebellar hypoplasia. Orphanet J Rare Dis , 6, 50. PMID: 21749694 DOI.

Journals

Reviews

Shoja MM, Jensen CJ, Ramdhan R, Chern J, Oakes WJ & Tubbs RS. (2018). Embryology of the Craniocervical Junction and Posterior Cranial Fossa Part II: Embryogenesis of the hindbrain. Clin Anat , , . PMID: 29344994 DOI.

Aldinger KA & Doherty D. (2016). The genetics of cerebellar malformations. Semin Fetal Neonatal Med , 21, 321-32. PMID: 27160001 DOI.

Butts T, Green MJ & Wingate RJ. (2014). Development of the cerebellum: simple steps to make a 'little brain'. Development , 141, 4031-41. PMID: 25336734 DOI.

Voogd J. (2012). A note on the definition and the development of cerebellar Purkinje cell zones. Cerebellum , 11, 422-5. PMID: 22396330 DOI.

Roussel MF & Hatten ME. (2011). Cerebellum development and medulloblastoma. Curr. Top. Dev. Biol. , 94, 235-82. PMID: 21295689 DOI.

Ten Donkelaar HJ & Lammens M. (2009). Development of the human cerebellum and its disorders. Clin Perinatol , 36, 513-30. PMID: 19732611 DOI.

Moldrich RX, Dauphinot L, Laffaire J, Rossier J & Potier MC. (2007). Down syndrome gene dosage imbalance on cerebellum development. Prog. Neurobiol. , 82, 87-94. PMID: 17408845 DOI.

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Terms

  • 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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Keith A. Human Embryology and Morphology. (1902) London: Edward Arnold.

The Hind Brain

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

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Cite this page: Hill, M.A. (2018, December 9) Embryology Neural - Cerebellum Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Neural_-_Cerebellum_Development

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