Neural - Cerebellum Development

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Introduction

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

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.


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.


Historic Links: Historic - The Cerebellum


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 | 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

  • 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 [3] "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. The cell-surface marker Neph3 enabled us to carry out timed prospective selection of Purkinje cell progenitors, which generated morphologically characteristic neurons with highly arborized dendrites that expressed mature Purkinje cell-specific markers such as the glutamate receptor subunit GluRδ2. Similar to mature Purkinje cells, these neurons also showed characteristic spontaneous and repeated action potentials and their postsynaptic excitatory potentials were generated exclusively through nonNMDA glutamate receptors. Fetal transplantation of precursors isolated by fluorescence-activated cell sorting showed orthotopic integration of the grafted neurons into the Purkinje cell layer with their axons extending to the deep cerebellar nuclei and dendrites receiving climbing and parallel fibers. This selective preparation of bona fide Purkinje cells should aid future investigation of this important neuron."

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

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.[4]

  • 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.


Historic Description

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. (text from Gray's Anatomy 1918)

Early Brain Vesicles

Primary Vesicles

CNS primary vesicles.jpg

Secondary Vesicles

CNS secondary vesicles.jpg

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.

Cerebellum Images

Abnormalities

Foliation Defects

Mouse cerebellar foliation defects.jpg

Mouse Cerebellar Foliation Defects[5]

(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)[6]

Pontocerebellar Hypoplasia (PCH) are very rare, inherited progressive neurodegenerative disorders with prenatal onset (for recent review see[6]). 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 <pubmed>21858122</pubmed>| PLoS One
  2. <pubmed>11724815</pubmed>| PMC2150878 | J Cell Biol.
  3. <pubmed>20835252</pubmed>
  4. ,pubmed>21380713</pubmed>
  5. <pubmed>21437245</pubmed>| PLoS One.
  6. 6.0 6.1 <pubmed>21749694</pubmed>| Orphanet J Rare Dis.

Journals

Reviews

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

Articles

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

Search PubMed

Search Pubmed: Cerebellum Embryology | Cerebellum Development | Medulloblastoma


Glossary Links

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Cite this page: Hill, M.A. (2019, December 7) Embryology Neural - Cerebellum Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Neural_-_Cerebellum_Development

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G