Neural - Cerebrum Development

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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 (cerebral cortex) as it is generally recognised. Though the cerebrum includes the cerebral cortex and the subcortical structures (hippocampus, basal ganglia, and olfactory bulb). The adult cerebral cortex like other neural structures has a laminar organisation, the mammalian neocortex consists of six layers, while the reptilian and avian cortices have only three layers (equivalent to mammalian layers I, V and VI). The adult human cerebrum contains about 16,340,000,000 ± 2,170,000,000 (sixteen billion three hundred forty million) neurons and 60,840,000,000 ± 7,020,000,000 other cell types.[2]

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.

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
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 | Postnatal | Postnatal - Neural Examination | Histology | Historic Neural | Category:Neural

Some Recent Findings

  • The LPA-LPA4 axis is required for establishment of bipolar morphology and radial migration of newborn cortical neurons[3] "Neurons in the developing neocortex undergo radial migration, a process that is coupled with their precise passage from multipolar to bipolar shape. The cell-extrinsic signals that govern this transition are, however, poorly understood. Here, we find that lysophosphatidic acid (LPA) signaling contributes to the establishment of a bipolar shape in mouse migratory neurons through LPA receptor 4 (LPA4)."
  • Development of the sensorimotor cortex in the human fetus: a morphological description[4] "Twenty-one human fetal brains from 13 to 28 gestational weeks were studied macroscopically to describe the morphological stages of sulcal and gyral development in the sensorimotor cortex....Four chronological stages of sensorimotor cortex development were defined: stage 1: appearance at 18-19 gestational weeks (GWs) of the inferior part of the central cerebral sulcus; stage 2: development of the pericentral lateral regions and the beginning of opercularization at 20-22 GWs; stage 3: development of parietal and temporal cortices and the covering of the postcentral insular region at 24-26 GWs; and finally stage 4: maturation of the central cerebral regions at 27-28 GWs."
More recent papers  
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Search term: Cerebral Cortex Embryology

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Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Local tissue growth patterns underlying normal fetal human brain gyrification quantified in utero[5] "we applied recent advances in fetal MRI motion correction and computational image analysis techniques to 40 normal fetal human brains covering a period of primary sulcal formation (20-28 gestational weeks). Growth patterns were mapped by quantifying tissue locations that were expanding more or less quickly than the overall cerebral growth rate, which reveal increasing structural complexity. We detected increased local relative growth rates in the formation of the precentral and postcentral gyri, right superior temporal gyrus, and opercula, which differentiated between the constant growth rate in underlying cerebral mantle and the accelerating rate in the cortical plate undergoing folding. Analysis focused on the cortical plate revealed greater volume increases in parietal and occipital regions compared to the frontal lobe. Cortical plate growth patterns constrained to narrower age ranges showed that gyrification, reflected by greater growth rates, was more pronounced after 24 gestational weeks. Local hemispheric volume asymmetry was located in the posterior peri-Sylvian area associated with structural lateralization in the mature brain."
  • Development of laminar organization of the fetal cerebrum[6] "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."
  • Correlation of diffusion tensor imaging with histology in the developing human frontal cerebrum[7] "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 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

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[8]

Neural- cortex Cajal drawing 01.jpg

Cortical layers in a historic drawing by Cajal.

Brain histology 01.jpg

Adult mouse cortex


I molecular layer - few neurons and mainly of extensions of apical dendrites and horizontally-oriented axons.


II external granular layer - small pyramidal neurons and many stellate neurons.



III external pyramidal layer - mainly small and medium-size pyramidal neurons, some non-pyramidal neurons with vertically-oriented intracortical axons.



IV internal granular layer - different types of stellate and pyramidal neurons.



V internal pyramidal layer - large pyramidal neurons.




VI multiform layer - few large pyramidal neurons and many small spindle-like pyramidal and multiform neurons.

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.[8]

Molecular

Mouse adult cortex[9]
  • Fgfr1 and Fgfr2 - control excitatory cortical neuron development within the entire cerebral cortex.[10]
  • Fgfr2 - proper formation of the medial prefrontal cortex (mPFC).[10]
  • MARCKS - (myristoylated alanine-rich C-kinase substrate protein) a cellular substrate for PKC modulates radial glial placement and expansion.[11]
  • MicroRNA - noncoding RNAs that regulate mRNA expression, highly expressed during development.[12]
  • Wnt - contribute to the production of basal progenitors (non-surface dividing or intermediate progenitors).[13]

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.[14]

Human Timeline:

  • 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

Cerebral Vascular Development

Overview cartoon Early vascular changes
Cerebral brain artery development 01.jpg Cerebral brain artery development 01.jpg

Chronological development of cerebral brain arteries initially with the rise of the internal carotid artery and subsequently with the development of the posterior circulation.[15]

Links: Blood Vessel Development | Head Development

Abnormalities

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


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.[16]

Schizencephaly

Abnormal organization

References

  1. Habas PA, Kim K, Rousseau F, Glenn OA, Barkovich AJ & Studholme C. (2010). Atlas-based segmentation of developing tissues in the human brain with quantitative validation in young fetuses. Hum Brain Mapp , 31, 1348-58. PMID: 20108226 DOI.
  2. Herculano-Houzel S, Catania K, Manger PR & Kaas JH. (2015). Mammalian Brains Are Made of These: A Dataset of the Numbers and Densities of Neuronal and Nonneuronal Cells in the Brain of Glires, Primates, Scandentia, Eulipotyphlans, Afrotherians and Artiodactyls, and Their Relationship with Body Mass. Brain Behav. Evol. , 86, 145-63. PMID: 26418466 DOI.
  3. Kurabayashi N, Tanaka A, Nguyen MD & Sanada K. (2018). The LPA-LPA4 axis is required for establishment of bipolar morphology and radial migration of newborn cortical neurons. Development , 145, . PMID: 30217809 DOI.
  4. Afif A, Trouillas J & Mertens P. (2015). Development of the sensorimotor cortex in the human fetus: a morphological description. Surg Radiol Anat , 37, 153-60. PMID: 24972575 DOI.
  5. Rajagopalan V, Scott J, Habas PA, Kim K, Corbett-Detig J, Rousseau F, Barkovich AJ, Glenn OA & Studholme C. (2011). Local tissue growth patterns underlying normal fetal human brain gyrification quantified in utero. J. Neurosci. , 31, 2878-87. PMID: 21414909 DOI.
  6. Zhang Z, Liu S, Lin X, Teng G, Yu T, Fang F & Zang F. (2011). Development of laminar organization of the fetal cerebrum at 3.0T and 7.0T: a postmortem MRI study. Neuroradiology , 53, 177-84. PMID: 20981415 DOI.
  7. Trivedi R, Husain N, Rathore RK, Saksena S, Srivastava S, Malik GK, Das V, Pradhan M, Pandey CM & Gupta RK. (2009). Correlation of diffusion tensor imaging with histology in the developing human frontal cerebrum. Dev. Neurosci. , 31, 487-96. PMID: 19622880 DOI.
  8. 8.0 8.1 <pubmed>20668538</pubmed>| PLoS Biol.
  9. <pubmed>19812240</pubmed>| PMC2871377
  10. 10.0 10.1 <pubmed>20410112</pubmed>
  11. <pubmed>19666823</pubmed>
  12. <pubmed>19914179</pubmed>
  13. <pubmed>20215343</pubmed>
  14. <pubmed>11778993</pubmed>
  15. <pubmed>26060802</pubmed>| J Stroke.
  16. <pubmed>19465910</pubmed>

Reviews

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

Articles

<pubmed>23727529</pubmed> <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. (2019, July 23) 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 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G