scholarly journals Immunohistochemical markers of neural progenitor cells in the early embryonic human cerebral cortex

2016 ◽  
Vol 60 (1) ◽  
Author(s):  
L. Vinci ◽  
A. Ravarino ◽  
V. Fanos ◽  
A.G. Naccarato ◽  
G. Senes ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Ventricular Zone ◽  
Cortical Plate ◽  
Human Embryos ◽  
Human Cerebral Cortex ◽  
Radial Glial Cells ◽  
Immunohistochemical Markers ◽  
Formalin Fixed Paraffin Embedded

<p>The development of the human central nervous system represents a delicate moment of embryogenesis. The purpose of this study was to analyze the expression of multiple immunohistochemical markers in the stem/progenitor cells in the human cerebral cortex during the early phases of development.  To this end, samples from cerebral cortex were obtained from 4 human embryos of 11 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained with several markers including GFAP, WT1, Nestin, Vimentin, CD117, S100B, Sox2, PAX2, PAX5, Tβ4, Neurofilament, CD44, CD133, Synaptophysin and Cyclin D1. Our study shows the ability of the different immunohistochemical markers to evidence different zones of the developing human cerebral cortex, allowing the identification of the multiple stages of differentiation of neuronal and glial precursors. Three important markers of radial glial cells are evidenced in this early gestational age: Vimentin, Nestin and WT1. Sox2 was expressed by the stem/progenitor cells of the ventricular zone, whereas the postmitotic neurons of the cortical plate were immunostained by PAX2 and NSE. Future studies are needed to test other important stem/progenitor cells markers and to better analyze differences in the immunohistochemical expression of these markers during gestation.</p>

scholarly journals Roots of the Malformations of Cortical Development in the Cell Biology of Neural Progenitor Cells

2022 ◽  
Vol 15 ◽  
Author(s):  
Chiara Ossola ◽  
Nereo Kalebic
Keyword(s):  
Cerebral Cortex ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Cortical Development ◽  
Neural Progenitor ◽  
Autism Spectrum ◽  
Model Systems ◽  
Cortical Plate ◽  
Malformations Of Cortical Development ◽  
Brain Functions

The cerebral cortex is a structure that underlies various brain functions, including cognition and language. Mammalian cerebral cortex starts developing during the embryonic period with the neural progenitor cells generating neurons. Newborn neurons migrate along progenitors’ radial processes from the site of their origin in the germinal zones to the cortical plate, where they mature and integrate in the forming circuitry. Cell biological features of neural progenitors, such as the location and timing of their mitoses, together with their characteristic morphologies, can directly or indirectly regulate the abundance and the identity of their neuronal progeny. Alterations in the complex and delicate process of cerebral cortex development can lead to malformations of cortical development (MCDs). They include various structural abnormalities that affect the size, thickness and/or folding pattern of the developing cortex. Their clinical manifestations can entail a neurodevelopmental disorder, such as epilepsy, developmental delay, intellectual disability, or autism spectrum disorder. The recent advancements of molecular and neuroimaging techniques, along with the development of appropriate in vitro and in vivo model systems, have enabled the assessment of the genetic and environmental causes of MCDs. Here we broadly review the cell biological characteristics of neural progenitor cells and focus on those features whose perturbations have been linked to MCDs.

scholarly journals Neural progenitor cells mediated by H2A.Z.2 regulate microglial development via Cxcl14 in the embryonic brain

2019 ◽  
Vol 116 (48) ◽  
pp. 24122-24132 ◽  
Author(s):  
Zhongqiu Li ◽  
Yanxin Li ◽  
Jianwei Jiao
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Ventricular Zone ◽  
Neural Progenitor ◽  
The Central Nervous System ◽  
Microglial Development

Microglia, the resident immune cells of the central nervous system, play an important role in the brain. Microglia have a special spatiotemporal distribution during the development of the cerebral cortex. Neural progenitor cells (NPCs) are the main source of neural-specific cells in the early brain. It is unclear whether NPCs affect microglial development and what molecular mechanisms control early microglial localization. H2A.Z.2, a histone variant of H2A, has a key role in gene expression regulation, genomic stability, and chromatin remodeling, but its function in brain development is not fully understood. Here, we found that the specific deletion of H2A.Z.2 in neural progenitor cells led to an abnormal increase in microglia in the ventricular zone/subventricular zone (VZ/SVZ) of the embryonic cortex. Mechanistically, H2A.Z.2 regulated microglial development by incorporating G9a into the promoter region of Cxcl14 and promoted H3k9me2 modification to inhibit the transcription of Cxcl14 in neural progenitor cells. Meanwhile, we found that the deletion of H2A.Z.2 in microglia itself had no significant effect on microglial development in the early cerebral cortex. Our findings demonstrate a key role of H2A.Z.2 in neural progenitor cells in controlling microglial development and broaden our knowledge of 2 different types of cells that may affect each other through crosstalk in the central nervous system.

Presenilin-1 regulates neuronal differentiation during neurogenesis

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2593-2606 ◽  
Author(s):  
M. Handler ◽  
X. Yang ◽  
J. Shen
Keyword(s):  
Cell Death ◽  
Progenitor Cells ◽  
Neuronal Differentiation ◽  
Cell Fate ◽  
Neural Progenitor Cells ◽  
Apoptotic Cell ◽  
Ventricular Zone ◽  
Neural Progenitor ◽  
Apoptotic Cell Death ◽  
Presenilin 1

Mutations in Presenilin-1 (PS1) are a major cause of familial Alzheimer's disease. Our previous studies showed that PS1 is required for murine neural development. Here we report that lack of PS1 leads to premature differentiation of neural progenitor cells, indicating a role for PS1 in a cell fate decision between postmitotic neurons and neural progenitor cells. Neural proliferation and apoptotic cell death during neurogenesis are unaltered in PS1(−/−) mice, suggesting that the reduction in the neural progenitor cells observed in the PS1(−/−) brain is due to premature differentiation of progenitor cells, rather than to increased apoptotic cell death or decreased cell proliferation. In addition, the premature neuronal differentiation in the PS1(−/−) brain is associated with aberrant neuronal migration and disorganization of the laminar architecture of the developing cerebral hemisphere. In the ventricular zone of PS1(−/−) mice, expression of the Notch1 downstream effector gene Hes5 is reduced and expression of the Notch1 ligand Dll1 is elevated, whereas expression of Notch1 is unchanged. The level of Dll1 transcripts is also increased in the presomitic mesoderm of PS1(−/−) embryos, while the level of Notch1 transcripts is unchanged, in contrast to a previous report (Wong et al., 1997, Nature 387, 288–292). These results provide direct evidence that PS1 controls neuronal differentiation in association with the downregulation of Notch signalling during neurogenesis.

Stromal derived factor-1α in hippocampus radial glial cells in vitro regulates the migration of neural progenitor cells

2015 ◽  
Vol 39 (6) ◽  
pp. 750-758 ◽  
Author(s):  
Hui Ding ◽  
Guo-Hua Jin ◽  
Lin-Qing Zou ◽  
Xiao-Qing Zhang ◽  
Hao-Ming Li ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Glial Cells ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Radial Glial Cells ◽  
Radial Glial

scholarly journals Mammalian Fat and Dachsous cadherins regulate apical membrane organization in the embryonic cerebral cortex

2009 ◽  
Vol 185 (6) ◽  
pp. 959-967 ◽  
Author(s):  
Takashi Ishiuchi ◽  
Kazuyo Misaki ◽  
Shigenobu Yonemura ◽  
Masatoshi Takeichi ◽  
Takuji Tanoue
Keyword(s):  
Cerebral Cortex ◽  
Plasma Membrane ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Apical Membrane ◽  
Neural Progenitor ◽  
Apical Plasma Membrane ◽  
Cell Contact ◽  
Membrane Organization ◽  
A Cell

Compartmentalization of the plasma membrane in a cell is fundamental for its proper functions. In this study, we present evidence that mammalian Fat4 and Dachsous1 cadherins regulate the apical plasma membrane organization in the embryonic cerebral cortex. In neural progenitor cells of the cortex, Fat4 and Dachsous1 were concentrated together in a cell–cell contact area positioned more apically than the adherens junction (AJ). These molecules interacted in a heterophilic fashion, affecting their respective protein levels. We further found that Fat4 associated and colocalized with the Pals1 complex. Ultrastructurally, the apical junctions of the progenitor cells comprised the AJ and a stretch of plasma membrane apposition extending apically from the AJ, which positionally corresponded to the Fat4–Dachsous1-positive zone. Depletion of Fat4 or Pals1 abolished this membrane apposition. These results highlight the importance of the Fat4–Dachsous1–Pals1 complex in organizing the apical membrane architecture of neural progenitor cells.

Promoter-targeted selection and isolation of neural progenitor cells from the adult human ventricular zone

2000 ◽  
Vol 59 (3) ◽  
pp. 321-331 ◽  
Author(s):  
Neeta S. Roy ◽  
Abdellatif Benraiss ◽  
Su Wang ◽  
Richard A.R. Fraser ◽  
Robert Goodman ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Ventricular Zone ◽  
Neural Progenitor ◽  
Adult Human

scholarly journals Intraventricular IL-17A Administration Activates Microglia and Alters Their Localization in the Mouse Embryo Cerebral Cortex

2020 ◽  
Author(s):  
Tetsuya Sasaki ◽  
Saki Tome ◽  
Yosuke Takei
Keyword(s):  
Cerebral Cortex ◽  
Neural Progenitor Cells ◽  
Ventricular Zone ◽  
Fetal Brain ◽  
Autism Spectrum ◽  
T Helper 17 ◽  
Maternal Immune Activation ◽  
Interleukin 17A ◽  
Cortical Dysgenesis ◽  
Behavioral Abnormalities

Abstract Viral infection during pregnancy has been suggested to increase the probability of autism spectrum disorder (ASD) in offspring via the phenomenon of maternal immune activation (MIA). This has been modeled in rodents. Maternal T helper 17 cells and the effector cytokine, interleukin 17A (IL-17A), play a central role in MIA-induced behavioral abnormalities and cortical dysgenesis, termed cortical patch. However, it is unclear how IL-17A acts on fetal brain cells to cause ASD pathologies. To assess the effect of IL-17A on cortical development, we directly administered IL-17A into the lateral ventricles of the fetal mouse brain. We analyzed injected brains focusing on microglia, which express IL-17A receptors. We found that IL-17A activated microglia and altered their localization in the cerebral cortex. Our data indicate that IL-17A activates cortical microglia, which leads to a cascade of ASD-related brain pathologies, including excessive phagocytosis of neural progenitor cells in the ventricular zone.

scholarly journals Cortical upper layer neurons derive from the subventricular zone as indicated bySvet1gene expression

Development ◽  
2001 ◽  
Vol 128 (11) ◽  
pp. 1983-1993 ◽  
Author(s):  
Victor Tarabykin ◽  
Anastassia Stoykova ◽  
Natalia Usman ◽  
Peter Gruss
Keyword(s):  
Cerebral Cortex ◽  
Molecular Markers ◽  
Cortical Neurons ◽  
Ventricular Zone ◽  
Underlying Mechanism ◽  
Cdna Libraries ◽  
Cortical Plate ◽  
Cortical Layers ◽  
Proliferating Cells ◽  
Expression Domain

The cerebral cortex is composed of a large variety of different neuron types. All cortical neurons, except some interneurons, are born in two proliferative zones, the cortical ventricular (VZ) and subventricular (SVZ) zones. The relative contribution of both proliferative zones to the generation of the diversity of the cortical neurons is not well understood. To further dissect the underlying mechanism, molecular markers specific for the SVZ are required. Towards this end we performed a subtraction of cDNA libraries, generated from E15.5 and E18.5 mouse cerebral cortex. A novel cDNA, Svet1, was cloned which was specifically expressed in the proliferating cells of the SVZ but not the VZ. The VZ is marked by the expression of the Otx1 gene. Later in development, Svet1 and Otx1 were expressed in subsets of cells of upper (II-IV) and deep (V-VI) layers, respectively. In the reeler cortex, where the layers are inverted, Svet1 and Otx1 label precursors of the upper and deeper layers, respectively, in their new location. Interestingly, in the Pax6/small eye mutant, Svet1 activity was abolished in the SVZ and in the upper part of the cortical plate while the Otx1 expression domain remained unchanged. Therefore, using Svet1 and Otx1 as cell-type-specific molecular markers for the upper and deep cortical layers we conclude that the Sey mutation affects predominantly the differentiation of the SVZ cells that fail to migrate into the cortical plate. The abnormality of the SVZ coincides with the absence of upper layer cells in the cortex. Taken together our data suggest that while the specification of deep cortical layers occurs in the ventricular zone, the SVZ is important for the proper specification of upper layers.

Tangential migration of neurons in the developing cerebral cortex

Development ◽  
1995 ◽  
Vol 121 (7) ◽  
pp. 2165-2176 ◽  
Author(s):  
N.A. O'Rourke ◽  
D.P. Sullivan ◽  
C.E. Kaznowski ◽  
A.A. Jacobs ◽  
S.K. McConnell
Keyword(s):  
Cerebral Cortex ◽  
Neuronal Migration ◽  
Ventricular Zone ◽  
Brain Slices ◽  
Cortical Plate ◽  
Tangential Migration ◽  
Cortical Regions ◽  
Intact Cortex ◽  
Migrating Cells

The mammalian cerebral cortex is divided into functionally distinct areas. Although radial patterns of neuronal migration have been thought to be essential for patterning these areas, direct observation of migrating cells in cortical brain slices has revealed that cells follow both radial and nonradial pathways as they travel from their sites of origin in the ventricular zone out to their destinations in the cortical plate (O'Rourke, N.A., Dailey, M.E., Smith, S.J. and McConnell, S.K. (1992) Science 258, 299–302). These findings suggested that neurons may not be confined to radial migratory pathways in vivo. Here, we have examined the patterns of neuronal migration in the intact cortex. Analysis of the orientations of [3H]thymidine-labeled migrating cells suggests that nonradial migration is equally common in brain slices and the intact cortex and that it increases during neurogenesis. Additionally, cells appear to follow nonradial trajectories at all levels of the developing cerebral wall, suggesting that tangential migration may be more prevalent than previously suspected from the imaging studies. Immunostaining with neuron-specific antibodies revealed that many tangentially migrating cells are young neurons. These results suggest that tangential migration in the intact cortex plays a pivotal role in the tangential dispersion of clonally related cells revealed by retroviral lineage studies (Walsh, C. and Cepko, C. L. (1992) Science 255, 434–440). Finally, we examined possible substrata for nonradial migration in dorsal cortical regions where the majority of glia extend radially. Using confocal and electron microscopy, we found that nonradially oriented cells run perpendicular to glial processes and make glancing contacts with them along their leading processes. Thus, if nonradial cells utilize glia as a migratory substratum they must glide across one glial fiber to another. Examination of the relationships between migratory cells and axons revealed axonal contacts with both radial and nonradial cells. These results suggest that nonradial cells use strategies and substrata for migration that differ from those employed by radial cells.

Sign in / Sign up

Export Citation Format

Share Document