Talk:Neural - Cerebrum Development

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Cite this page: Hill, M.A. (2021, April 11) Embryology Neural - Cerebrum Development. Retrieved from


Wang XL, Ma YX, Xu RJ, Ma JJ, Zhang HC, Qi SB, Xu JH, Qin XZ, Zhang HN, Liu CM, Chen JQ, Li B, Yang HL & Saijilafu. (2020). c-Myc controls the fate of neural progenitor cells during cerebral cortex development. J. Cell. Physiol. , 235, 4011-4021. PMID: 31625158 DOI.

c-Myc controls the fate of neural progenitor cells during cerebral cortex development.

Abstract The anatomical structure of the mammalian cerebral cortex is the essential foundation for its complex neural activity. This structure is developed by proliferation, differentiation, and migration of neural progenitor cells (NPCs), the fate of which is spatially and temporally regulated by the proper gene. This study was used in utero electroporation and found that the well-known oncogene c-Myc mainly promoted NPCs' proliferation and their transformation into intermediate precursor cells. Furthermore, the obtained results also showed that c-Myc blocked the differentiation of NPCs to postmitotic neurons, and the expression of telomere reverse transcriptase was controlled by c-Myc in the neocortex. These findings indicated c-Myc as a key regulator of the fate of NPCs during the development of the cerebral cortex. © 2019 Wiley Periodicals, Inc. KEYWORDS: c-Myc; cerebral cortex; neural progenitor cells PMID: 31625158 DOI: 10.1002/jcp.29297

Dopamine as a growth differentiation factor in the mammalian brain

Neural Regen Res. 2020 Mar;15(3):390-393. doi: 10.4103/1673-5374.266052.

Ohira K1. Author information 1 Laboratory of Nutritional Brain Science, Department of Food Science and Nutrition, Mukogawa Women's University, Nishinomiya, Hyogo, Japan. Abstract The catecholamine, dopamine, plays an important role in the central nervous system of mammals, including executive functions, motor control, motivation, arousal, reinforcement, and reward. Dysfunctions of the dopaminergic system lead to diseases of the brains, such as Parkinson's disease, Tourette's syndrome, and schizophrenia. In addition to its fundamental role as a neurotransmitter, there is evidence for a role as a growth differentiation factor during development. Recent studies suggest that dopamine regulates the development of γ-aminobutyric acidergic interneurons of the cerebral cortex. Moreover, in adult brains, dopamine increases the production of new neurons in the hippocampus, suggesting the promoting effect of dopamine on proliferation and differentiation of neural stem cells and progenitor cells in the adult brains. In this mini-review, I center my attention on dopaminergic functions in the cortical interneurons during development and further discuss cell therapy against neurodegenerative diseases. KEYWORDS: GABA; adult neurogenesis; cerebral cortex; dopamine; medial ganglionic eminence; migration; striatum; γ-aminobutyric acidergic interneuron PMID: 31571646 DOI: 10.4103/1673-5374.266052


J Neurosci Res. 2019 Dec;97(12):1624-1635. doi: 10.1002/jnr.24503. Epub 2019 Jul 28. Developmental origins of cortical hyperexcitability in Huntington's disease: Review and new observations. Cepeda C1, Oikonomou KD1, Cummings D1, Barry J1, Yazon VW1, Chen DT1, Asai J1, Williams CK2,3, Vinters HV2,3. Author information 1 IDDRC, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California. 2 Section of Neuropathology, Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California. 3 Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. Abstract Huntington's disease (HD), an inherited neurodegenerative disorder that principally affects striatum and cerebral cortex, is generally thought to have an adult onset. However, a small percentage of cases develop symptoms before 20 years of age. This juvenile variant suggests that brain development may be altered in HD. Indeed, recent evidence supports an important role of normal huntingtin during embryonic brain development and mutations in this protein cause cortical abnormalities. Functional studies also demonstrated that the cerebral cortex becomes hyperexcitable with disease progression. In this review, we examine clinical and experimental evidence that cortical development is altered in HD. We also provide preliminary evidence that cortical pyramidal neurons from R6/2 mice, a model of juvenile HD, are hyperexcitable and display dysmorphic processes as early as postnatal day 7. Further, some symptomatic mice present with anatomical abnormalities reminiscent of human focal cortical dysplasia, which could explain the occurrence of epileptic seizures in this genetic mouse model and in children with juvenile HD. Finally, we discuss recent treatments aimed at correcting abnormal brain development. © 2019 Wiley Periodicals, Inc. KEYWORDS: Huntington's disease; cortical development; cortical dysplasia; electrophysiology; epilepsy PMID: 31353533 PMCID: PMC6801077 [Available on 2020-06-01] DOI: 10.1002/jnr.24503


The LPA-LPA4 axis is required for establishment of bipolar morphology and radial migration of newborn cortical neurons

Development. 2018 Sep 14;145(17). pii: dev162529. doi: 10.1242/dev.162529.

Kurabayashi N1, Tanaka A1, Nguyen MD2, Sanada K3.


Newborn 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). LPA4 is robustly expressed in migratory neurons. LPA4-depleted neurons show impaired multipolar-to-bipolar transition and become arrested in their migration. Further, LPA4-mediated LPA signaling promotes formation of the pia-directed process in primary neurons overlaid on neocortical slices. In addition, LPA4 depletion is coupled with altered actin organization as well as with destabilization of the F-actin-binding protein filamin A (FlnA). Finally, overexpression of FlnA rescues the morphology and migration defects of LPA4-depleted neurons. Thus, the LPA-LPA4 axis regulates bipolar morphogenesis and radial migration of newborn cortical neurons via remodeling of the actin cytoskeleton. KEYWORDS: Developing neocortex; G-protein-coupled receptor; Lysophosphatidic acid; Mouse; Neuronal migration PMID: 30217809 DOI: 10.1242/dev.162529


Chin Med J (Engl). 2017 Apr 20;130(8):920-928. doi: 10.4103/0366-6999.204114. Ultrasonographic Characteristics of Cortical Sulcus Development in the Human Fetus between 18 and 41 Weeks of Gestation. Chen X1, Li SL1, Luo GY2, Norwitz ER3, Ouyang SY4, Wen HX1, Yuan Y1, Tian XX5, He JM1. Author information Abstract BACKGROUND: Fetal brain development is a complicated process that continues throughout pregnancy. Fetal sulcus development has typical morphological features. Assessment of fetal sulcus development to understand the cortical maturation and development by prenatal ultrasound has become widespread. This study aimed to explore a reliable method to assess cortical sulcus and to describe the normal sonographic features of cortical sulcus development in the human fetus between 18 and 41 weeks of gestation. METHODS: A cross-sectional study was designed to examine the fetal cortical sulcus development at 18-41 weeks of gestation. Ultrasound was used to examine the insula, sylvian fissure (SF), parieto-occipital fissure (POF), and calcarine fissure (CF). Bland-Altman plots were used for assessing the concordance, and the intraclass correlation coefficient was used for assessing the reliability. RESULTS: SF images were successfully obtained in 100% of participants at 22 weeks of gestation, while the POF images and CF images could be obtained in 100% at 23 weeks of gestation and 24 weeks of gestation, respectively. The SF width, temporal lobe depth, POF depth, and the CF depth increased with the developed gestation. The width of uncovered insula and the POF angle decreased with the developed gestation. By 23 weeks of gestation, the insula was beginning to be covered. Moreover, it completed at 35 weeks of gestation. The intra- and inter-observer agreements showed consistent reproducibility. CONCLUSIONS: This study defined standard views of the fetal sulcus as well as the normal reference ranges of these sulcus measurements between 18 and 41 weeks of gestation. Such ultrasonographic measurements could be used to identify fetuses at risk of fetal neurological structural disorders. PMID: 28397721 PMCID: PMC5407038 DOI: 10.4103/0366-6999.204114


Development of the sensorimotor cortex in the human fetus: a morphological description

Surg Radiol Anat. 2014 Jun 28. [Epub ahead of print]

Afif A1, Trouillas J, Mertens P.


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. In particular, the morphological appearance of the pericentral lateral cortex (sensorimotor cortex) and opercula was noted, as well as the vascularization of these regions. The central cerebral sulci were the first macroscopical structures to be identified on the lateral surface of the human cerebral hemisphere. 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. These observations indicate the concomitance in the initiation of maturation of the pericentral cerebral cortices.

PMID 24972575

Fetal cerebral lobes development between 20 and 28 weeks gestational age: a postmortem MR study

Int J Dev Neurosci. 2014 Feb;32:23-7. doi: 10.1016/j.ijdevneu.2013.09.004. Epub 2013 Sep 20.

Yang L1, Chen L2, Qiu X2, Zhang Z3, Liu S4, Wang G2, Xiao L2, Lin X5.


To investigate the fetal cerebral lobes development between 20 and 28 weeks gestational age, 36 fetus specimen without CNS abnormality, with 4 fetuses in each gestation week, were scanned with 3.0T MR. Lobular parameters were measured, including the parenchyma thickness of the frontoparietal and the temporal lobes, the margin length of frontoparietal, the insula and the temporal lobes, the Sylvian fissure and the perimeter of hippocampus, on the plane perpendicular to the longitudinal axis of hippocampus body across the base of cerebral peduncle. The relative value of parenchyma thickness and the lobes' length ratios to the same side hemisphere were calculated and their correlation with gestational weeks was analyzed. All measured parameters were positively correlated with gestational age. No significant tendency was found for relative value of the parenchyma thickness (P>0.05). The temporal lobe length ratio increased while the frontoparietal ratio decreased before 24 weeks GA and then the two reversed. The Sylvian fissure length ratio increased (P<0.001) and the hippocampus decreased (P<0.001) throughout this period. In conclusion, the early fetal cerebrum lobes developed asynchronously during this period, the 24 weeks GA could be a turning point for cerebrum development pattern changing from primitive to mature. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved. KEYWORDS: Asynchrony; Cerebrum lobes; Development; MRI; Midtrimester

PMID 24060494


Spatial-temporal atlas of human fetal brain development during the early second trimester

Neuroimage. 2013 Nov 15;82:115-26. doi: 10.1016/j.neuroimage.2013.05.063. Epub 2013 May 31.

Zhan J1, Dinov ID, Li J, Zhang Z, Hobel S, Shi Y, Lin X, Zamanyan A, Feng L, Teng G, Fang F, Tang Y, Zang F, Toga AW, Liu S.


During the second trimester, the human fetal brain undergoes numerous changes that lead to substantial variation in the neonatal in terms of its morphology and tissue types. As fetal MRI is more and more widely used for studying the human brain development during this period, a spatiotemporal atlas becomes necessary for characterizing the dynamic structural changes. In this study, 34 postmortem human fetal brains with gestational ages ranging from 15 to 22 weeks were scanned using 7.0 T MR. We used automated morphometrics, tensor-based morphometry and surface modeling techniques to analyze the data. Spatiotemporal atlases of each week and the overall atlas covering the whole period with high resolution and contrast were created. These atlases were used for the analysis of age-specific shape changes during this period, including development of the cerebral wall, lateral ventricles, Sylvian fissure, and growth direction based on local surface measurements. Our findings indicate that growth of the subplate zone is especially striking and is the main cause for the lamination pattern changes. Changes in the cortex around Sylvian fissure demonstrate that cortical growth may be one of the mechanisms for gyration. Surface deformation mapping, revealed by local shape analysis, indicates that there is global anterior-posterior growth pattern, with frontal and temporal lobes developing relatively quickly during this period. Our results are valuable for understanding the normal brain development trajectories and anatomical characteristics. These week-by-week fetal brain atlases can be used as reference in in vivo studies, and may facilitate the quantification of fetal brain development across space and time. Copyright © 2013 Elsevier Inc. All rights reserved. KEYWORDS: Atlas; Fetal MRI; Human brain development; Second-trimester

PMID 23727529

Development of the fetal cerebral cortex in the second trimester: assessment with 7T postmortem MR imaging

AJNR Am J Neuroradiol. 2013 Jul;34(7):1462-7. doi: 10.3174/ajnr.A3406. Epub 2013 Feb 14.

Zhang Z1, Hou Z, Lin X, Teng G, Meng H, Zang F, Fang F, Liu S.


BACKGROUND AND PURPOSE: Few investigators have analyzed the fetal cerebral cortex with MR imaging of high magnetic strength. Our purpose was to document the sulcal development and obtain quantitative measurements of the fetal brain in the second trimester. MATERIALS AND METHODS: The brains of 69 fetal specimens, with GA 12-22 weeks, were first scanned on a 7T MR imaging scanner. Then the sequential development of the different fissures and sulci was analyzed, and quantitative measurements of the cerebral cortex were obtained. RESULTS: A new chronology of sulcal development during 12-22 weeks GA was summarized. Before 12 weeks, few sulci were present; by 16 weeks, many sulci were present. The 16th week could be considered the most intensive time point for sulcal emergence. Most sulci, except for the postcentral sulcus and intraparietal sulcus, were present by 22 weeks GA. Measurements of the fetal brains, each with different growth rates, linearly increased with GA, but no sexual dimorphisms or cerebral asymmetries were detected. CONCLUSIONS: The second trimester is the most important phase, during which most sulci are present and can be clearly shown on 7T postmortem MR imaging. It is apparent that the specific time during which neuropathologic features of sulci appear, previously thought to be well understood, should be redefined. Quantitative data provide assistance in the precise understanding of the immature brain. The present results are valuable in anatomic education, research, and assessment of normal brain development in the uterus.

PMID 23413246


Local tissue growth patterns underlying normal fetal human brain gyrification quantified in utero

J Neurosci. 2011 Feb 23;31(8):2878-87.

Rajagopalan V, Scott J, Habas PA, Kim K, Corbett-Detig J, Rousseau F, Barkovich AJ, Glenn OA, Studholme C. Source Biomedical Image Computing Group, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94143-0628, USA.


Existing knowledge of growth patterns in the living fetal human brain is based upon in utero imaging studies by magnetic resonance imaging (MRI) and ultrasound, which describe overall growth and provide mainly qualitative findings. However, formation of the complex folded cortical structure of the adult brain requires, in part, differential rates of regional tissue growth. To better understand these local tissue growth patterns, 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. These maps of fetal brain growth patterns construct a spatially specific baseline of developmental biomarkers with which to correlate abnormal development in the human.

PMID 21414909


Diffusion tensor imaging of the cortical plate and subplate in very-low-birth-weight infants

Pediatr Radiol. 2010 Aug;40(8):1397-404. Epub 2010 Mar 27.

Dudink J, Buijs J, Govaert P, van Zwol AL, Conneman N, van Goudoever JB, Lequin M.

Division of Neonatology, Department of Paediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. Abstract BACKGROUND: Many intervention studies in preterm infants aim to improve neurodevelopmental outcome, but short-term proxy outcome measurements are lacking. Cortical plate and subplate development could be such a marker.

OBJECTIVE: Our aim was to provide normal DTI reference values for the cortical plate and subplate of preterm infants.

MATERIALS AND METHODS: As part of an ongoing study we analysed diffusion tensor imaging (DTI) images of 19 preterm infants without evidence of injury on conventional MRI, with normal outcome (Bayley-II assessed at age 2), and scanned in the first 4 days of life. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values in the frontal and temporal subplate and cortical plate were measured in single and multiple voxel regions of interest (ROI) placed on predefined regions.

RESULTS: Using single-voxel ROIs, statistically significant inverse correlation was found between gestational age (GA) and FA of the frontal (r = -0.5938, P = 0.0058) and temporal (r = -0.4912, P = 0.0327) cortical plate. ADC values had a significant positive correlation with GA in the frontal (r = 0.5427, P = 0.0164) and temporal (r = 0.5540, P = 0.0138) subplate.

CONCLUSION: Diffusion tensor imaging allows in vivo exploration of the evolving cortical plate and subplate. We provide FA and ADC values of the subplate and cortical plate in very-low-birth-weight (VLBW) infants with normal developmental outcome that can be used as reference values.

Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

PMID: 20349230

Prox1 is required for granule cell maturation and intermediate progenitor maintenance during brain neurogenesis

PLoS Biol. 2010 Aug 17;8(8). pii: e1000460.

Lavado A, Lagutin OV, Chow LM, Baker SJ, Oliver G.

Department of Genetics & Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America. Abstract The dentate gyrus has an important role in learning and memory, and adult neurogenesis in the subgranular zone of the dentate gyrus may play a role in the acquisition of new memories. The homeobox gene Prox1 is expressed in the dentate gyrus during embryonic development and adult neurogenesis. Here we show that Prox1 is necessary for the maturation of granule cells in the dentate gyrus during development and for the maintenance of intermediate progenitors during adult neurogenesis. We also demonstrate that Prox1-expressing intermediate progenitors are required for adult neural stem cell self-maintenance in the subgranular zone; thus, we have identified a previously unknown non-cell autonomous regulatory feedback mechanism that controls adult neurogenesis in this region of the mammalian brain. Finally, we show that the ectopic expression of Prox1 induces premature differentiation of neural stem cells.

PMID: 20808958

Abnormal development of the cerebral cortex and cerebellum in the setting of lamin B2 deficiency

Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5076-81. Epub 2010 Feb 9.

Coffinier C, Chang SY, Nobumori C, Tu Y, Farber EA, Toth JI, Fong LG, Young SG.

Departments of Medicine and Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. Comment in:

Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6121-2. Abstract Nuclear lamins are components of the nuclear lamina, a structural scaffolding for the cell nucleus. Defects in lamins A and C cause an array of human diseases, including muscular dystrophy, lipodystrophy, and progeria, but no diseases have been linked to the loss of lamins B1 or B2. To explore the functional relevance of lamin B2, we generated lamin B2-deficient mice and found that they have severe brain abnormalities resembling lissencephaly, with abnormal layering of neurons in the cerebral cortex and cerebellum. This neuronal layering abnormality is due to defective neuronal migration, a process that is dependent on the organized movement of the nucleus within the cell. These studies establish an essential function for lamin B2 in neuronal migration and brain development.

PMID: 20145110

Repression of Fgf signaling by sprouty1-2 regulates cortical patterning in two distinct regions and times

J Neurosci. 2010 Mar 17;30(11):4015-23.

Faedo A, Borello U, Rubenstein JL.

Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, San Francisco, California 94158-2611, USA. Abstract A fundamental question in developmental biology is how signaling pathways establish a transcription factor code that controls cell proliferation, regional fate and cell fate. Morphogenesis of the rostral telencephalon is controlled in part by Fgf signaling from the rostral patterning center. How Fgf signaling is regulated in the telencephalon is critical for understanding cerebral cortex formation. Here we show that mouse Sprouty1 and Sprouty2 (Spry1-2), which encode negative feedback regulators of Fgf signaling, are affecting cortical proliferation, differentiation, and the expression of genes regulating progenitor identity in the ventricular zone. In addition, Spry2 has a later function in regulating the MAPK pathway, proliferation, and gene expression in the cortex at mid-neurogenesis. Finally, we provide evidence that Coup-TFI, a transcription factor that promotes caudal fate, does so through repressing Fgf signaling, in part by promoting Spry expression.

PMID: 20237272


Correlation of diffusion tensor imaging with histology in the developing human frontal cerebrum

Dev Neurosci. 2009;31(6):487-96. Epub 2009 Jul 20.

Trivedi R, Husain N, Rathore RK, Saksena S, Srivastava S, Malik GK, Das V, Pradhan M, Pandey CM, Gupta RK.

Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. Abstract 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.

Copyright 2009 S. Karger AG, Basel. PMID: 19622880