Neural - Cerebrum Development

From Embryology
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Introduction

Human embryo developing cortex (week 8, stage 22)
Human cerebrum and underlying ventricular development imaged by MRI[1]
Dev anat 01.jpg
Gray0677.jpg

The brain as it is generally recognised. The adult cerebral cortex like other neural structures has a laminar organization.

A simplified developmental sequence can be described as cell proliferation, cell migration, and finally cortical organization. In development, lamination occurs in an "inside-out" sequence earlier inside and later born neurons outside. The cortex is divided into areas which serve distinct functions including motor, sensory and cognitive processing. The lamination process requires a range of different signals including; Reelin (Reln, an extracellular protein), Disabled-1 (Dab1, an intracellular signaling molecule), and Cullin-5 (Cul5, an E3 ubiquitin ligase).

The cortex progenitor cell types are either neuron-restricted or bipotent (neuron-glial) progenitors that generate glial-restricted progenitors at mid- and late neurogenesis.

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Some Recent Findings

  • Correlation of diffusion tensor imaging with histology in the developing human frontal cerebrum[2] "Transient early cerebral laminar organization resulting from normal developmental events has been revealed in human beings through histology and imaging studies. DTI studies have postulated that the fractional anisotropy (FA)-based differentiation of different laminar structures reflects both differing cellular density over the glial fibers and fiber alignment in respective regions. The aim of this study was to correlate FA values in these transient zones with histology. Brain DTI was performed on 50 freshly aborted human fetuses with gestational ages (GA) ranging from 12 to 42 weeks. Regions of interest were placed on the cortical plate, subplate, intermediate and germinal matrix (GMx) zones of the frontal lobe to quantify FA values. Glial fibrillary acidic protein (GFAP), neurofilament (NF) and neuron-specific enolase (NSE) immunohistochemical analyses were performed for the cortical plate, intermediate zone and GMx. In the cortical plate, a significant positive correlation was observed between FA values and percentage area of GFAP expression in fetuses <or=28 weeks of GA (r = 0.56, p = 0.01). FA values showed a significant positive correlation with the percentage area of NF expression in the intermediate zone (r = 0.54, p = 0.05). A significant positive correlation was also observed between FA and the number of NSE-positive cells per mm(2) in the GMx (r = 0.76, p < 0.01) and subplate (r = 0.59, p = 0.03) zones. The results of our study suggest that the FA can be used as noninvasive marker of neurodevelopmental events in the frontal lobe of human fetal brain."
  • Development of laminar organization of the fetal cerebrum[3] "Heads of 131 fetal specimens of 14-40 weeks gestational age (GA) were scanned by 3.0T MRI. Eleven fetal specimens of 14-27 weeks GA were scanned by 7.0T MRI. On T(1)-weighted 3.0T MRI, layers could be visualized at 14 weeks GA and appeared clearer after 18 weeks GA. On 7.0T MRI, four zones could be recognized at 14 weeks GA. During 15-22 weeks GA, when laminar organization appeared typical, seven layers including the periventricular zone and external capsule fibers could be differentiated, which corresponded to seven zones in histological stained sections. At 23-28 weeks GA, laminar organization appeared less typical, and borderlines among them appeared obscured. After 30 weeks GA, it disappeared and turned into mature-like structures. The developing lamination appeared the most distinguishable at the parieto-occipital part of brain and peripheral regions of the hippocampus. The migrating thalamocortical afferents were probably delineated as a high signal layer located at the lower, middle, and upper part of the subplate zone at 16-28 weeks GA on T(1)-weighted 3.0T MRI."

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 (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

Early Brain Vesicles

Primary Vesicles

CNS primary vesicles.jpg

Secondary Vesicles

CNS secondary vesicles.jpg

Late Embryonic Brain

Stage 22 image 217.jpg

Human embryo developing cortex (Week 8, Carnegie stage 22)

  • small embryo shows approximate level of section.
  • insert top right shows whole head section.
  • small shaded box on whole section shows region of large image.
  • layer thicknesses are shown in microns.

Early Fetal Brain

Human- fetal week 10 head A.jpg Human- fetal week 10 head B.jpg
Human- fetal week 10 head C.jpg Human- fetal week 10 head D.jpg

The above images are from a week 10 human fetus.

Fetal Brain

Gray0654.jpg Gray0655.jpg Gray0658.jpg
Fetal brain (3 months) Fetal brain (4 months) Fetal brain (5 months)

Fissures are the major indentations, sulci (singular sulcus), that divide the brain surface into lobes and appear during fetal development as the brain grows. The images below show MRI analysis of the developing human fetal brain.

Brain fissure development 01.jpg

Brain fissure development 02.jpg

Brain fissure development 03.jpg


Links: Magnetic Resonance Imaging

Developmental Overview

Neural-development.jpg

Cortical Neurons

Telencephalon development signals[4]

Neural- cortex Cajal drawing 01.jpg

Cortical layers in a historic drawing by Cajal.

Cajal-Retzius Neurons

Cajal-Retzius (CR) cells are some of the earliest generated cortical neurons arising from restricted domains of the pallial ventricular zone, and then migrate from the borders of the developing pallium to cover the cortical primordium. These early forming neurons then control the radial migration of neurons and the formation of cortical layers. In mice, this has been shown by these cells secreting the extracellular glycoprotein Reelin (Reln) and it has been suggested that these cells also fine tune multiple signaling pathways underlying the regulation of cortical regionalization.[4]

Molecular

Mouse adult cortex[5]
  • Fgfr1 and Fgfr2 - control excitatory cortical neuron development within the entire cerebral cortex.[6]
  • Fgfr2 - proper formation of the medial prefrontal cortex (mPFC).[6]
  • MARCKS - (myristoylated alanine-rich C-kinase substrate protein) a cellular substrate for PKC modulates radial glial placement and expansion.[7]
  • MicroRNA - noncoding RNAs that regulate mRNA expression, highly expressed during development.[8]
  • Wnt - contribute to the production of basal progenitors (non-surface dividing or intermediate progenitors).[9]

Corpus Callosum

The corpus callosum is the area of the brain which connects the two cerebral hemispheres. Maximum increase in thickness and width of the corpus callosum occurred between 19 and 21 weeks' gestation.[10]


  • 74 days - callosal axons appear
  • 84 days - subdivisions of the genu and splenium can be identified
  • 115 days - adult morphology is seen


Agenesis of Corpus Callosum

Agenesis of the corpus callosum (ACC) is a partial or complete absence of the corpus callosum, a rare cerebral malformation.


Links: NINDS Information

Abnormalities

Hemimegalencephaly

Increased proliferation

Heterotopia

Ectopic migration

Lissencephaly

A malformations derived from abnormal neuronal migration leading to agyria (convolutions of the cerebral cortex are not fully formed) and pachygyria (convolutions of the cerebral cortex unusually thick ).

Pachygyria (Greek, pachy = "thick")

Microlissencephaly

Decreased proliferation

Polymicrogyria

Abnormal organization, numerous small gyri and a thick disorganized cortical plate lacking normal lamination, disruption of microtubule-based processes underlies a large spectrum of neuronal migration.[11]

Schizencephaly

Abnormal organization

References

  1. <pubmed>20108226</pubmed>
  2. <pubmed>19622880</pubmed>
  3. <pubmed>20981415</pubmed>
  4. 4.0 4.1 <pubmed>20668538</pubmed>| PLoS Biol.
  5. <pubmed>19812240</pubmed>| PMC2871377
  6. 6.0 6.1 <pubmed>20410112</pubmed>
  7. <pubmed>19666823</pubmed>
  8. <pubmed>19914179</pubmed>
  9. <pubmed>20215343</pubmed>
  10. <pubmed>11778993</pubmed>
  11. <pubmed>19465910</pubmed>

Reviews

<pubmed>19732610</pubmed> <pubmed>19763105</pubmed>

Articles

<pubmed>20161753</pubmed> <pubmed>20040495</pubmed> <pubmed>20410119</pubmed> <pubmed>20410112</pubmed> <pubmed>20215343</pubmed>

Search PubMed

Search Pubmed: Cerebrum Embryology | Cerebrum Development

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

  • Zagreb Neuroembryological Collection - contains more than 500 prenatal human brains stained with various classical neurohistological, as well as modern histochemical and immunohistochemical methods. The bank is located at the Croatian Institute for Brain Research. http://www.hiim.hr/nova

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Cite this page: Hill, M.A. (2024, March 29) Embryology Neural - Cerebrum Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Neural_-_Cerebrum_Development

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G