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.

scholarly journals Septin 14 Is Involved in Cortical Neuronal Migration via Interaction with Septin 4

2010 ◽  
Vol 21 (8) ◽  
pp. 1324-1334 ◽  
Author(s):  
Tomoyasu Shinoda ◽  
Hidenori Ito ◽  
Kaori Sudo ◽  
Ikuko Iwamoto ◽  
Rika Morishita ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Neuronal Migration ◽  
Cortical Neurons ◽  
Neuronal Development ◽  
Cell Cycle Control ◽  
Coiled Coil ◽  
Cortical Plate ◽  
Process Formation ◽  
Biochemical Analyses

Septins are a family of conserved guanosine triphosphate/guanosine diphosphate-binding proteins implicated in a variety of cellular functions such as cell cycle control and cytokinesis. Although several members of septin family, including Septin 14 (Sept14), are abundantly expressed in nervous tissues, little is known about their physiological functions, especially in neuronal development. Here, we report that Sept14 is strongly expressed in the cortical plate of developing cerebral cortex. Knockdown experiments by using the method of in utero electroporation showed that reduction of Sept14 caused inhibition of cortical neuronal migration. Whereas cDNA encoding RNA interference-resistant Sept14 rescued the migration defect, the C-terminal deletion mutant of Sept14 did not. Biochemical analyses revealed that C-terminal coiled-coil region of Sept14 interacts with Septin 4 (Sept4). Knockdown experiments showed that Sept4 is also involved in cortical neuronal migration in vivo. In addition, knockdown of Sept14 or Sept4 inhibited leading process formation in migrating cortical neurons. These results suggest that Sept14 is involved in neuronal migration in cerebral cortex via interaction with Sept4.

scholarly journals The dynamic interplay between ATP/ADP levels and autophagy sustain neuronal migration in vivo

2020 ◽  
Author(s):  
Bressan Cedric ◽  
Pecora Alessandra ◽  
Gagnon Dave ◽  
Snapyan Marina ◽  
Labrecque Simon ◽  
...  
Keyword(s):  
Cell Migration ◽  
Stationary Phase ◽  
Neuronal Migration ◽  
Stationary Phases ◽  
Focal Adhesions ◽  
Time Lapse ◽  
List Type ◽  
Atp Levels ◽  
Migrating Cells

AbstractCell migration is a dynamic process that entails extensive protein synthesis and recycling, structural remodeling, and a considerable bioenergetic demand. Autophagy is one of the pathways that maintain cellular homeostasis. Time-lapse imaging of autophagosomes and ATP/ADP levels in migrating cells in the rostral migratory stream of mice revealed that decrease in ATP levels force cells into the stationary phase and induce autophagy. Genetic impairment of autophagy in neuroblasts using either inducible conditional mice or CRISPR/Cas9 gene editing decreased cell migration due to the longer duration of the stationary phase. Autophagy is modulated in response to migration-promoting and inhibiting molecular cues and is required for the recycling of focal adhesions. Our results show that autophagy and energy consumption act in concert in migrating cells to dynamically regulate the pace and periodicity of the migratory and stationary phases in order to sustain neuronal migration.HighlightsADP levels dynamically change during cell migrationA decrease in ATP levels leads to cell pausing and autophagy induction via AMPKAutophagy is required to sustain neuronal migration by recycling focal adhesionsAutophagy level is dynamically modulated by migration-promoting and inhibiting cues

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.

scholarly journals Brain-synthesized estrogens regulate cortical migration in a sexually divergent manner

2019 ◽  
Author(s):  
Katherine J. Sellers ◽  
Matthew C.S. Denley ◽  
Atsushi Saito ◽  
Atsushi Kamiya ◽  
Deepak P. Srivastava
Keyword(s):  
Cerebral Cortex ◽  
Opposite Effect ◽  
Ventricular Zone ◽  
Cortical Plate ◽  
Local Synthesis ◽  
Male And Female ◽  
Sexual Dimorphisms ◽  
Female Mice ◽  
Males And Females

AbstractEstrogens play an important role in the sexual dimorphisms that occur during brain development, including the neural circuitry that underlies sex-typical and socio-aggressive behaviors. Aromatase, the enzyme responsible for the conversion of androgens to estrogens, is expressed at high levels during early development in both male and female cortices, suggesting a role for brain-synthesized estrogens during corticogenesis. This study investigated how the local synthesis of estrogens affects neurodevelopment of the cerebral cortex, and how this differs in males and females by knockdown expression of the Cyp19a1 gene, which encodes aromatase, between embryonic day 14.5 and postnatal day 0 (P0). The effects of Cyp19a1 knockdown on neural migration was then assessed. Aromatase was expressed in the developing cortex of both sexes, but at significantly higher levels in male than female mice. Under basal conditions, no obvious differences in cortical migration between male and female mice were observed. However, knockdown of Cyp19a1 increased the number GFP-positive cells in the cortical plate, with a concurrent decrease in the subventricular zone/ventricular zone in P0 male mice. The opposite effect was observed in females, with a significantly reduced number of GFP-positive cells migrating to the cortical plate. These findings have important implications for our understanding of the role of fetal steroids for neuronal migration during cerebral cortex development. Moreover, these data indicate that brain-synthesized estrogens regulate radial migration through distinct mechanisms in males and females.

scholarly journals Cell migration in the developing chick diencephalon

Development ◽  
1997 ◽  
Vol 124 (18) ◽  
pp. 3525-3533
Author(s):  
J.A. Golden ◽  
J.C. Zitz ◽  
K. McFadden ◽  
C.L. Cepko
Keyword(s):  
Cell Migration ◽  
Radial Glia ◽  
Sibling Relationships ◽  
Ventricular Zone ◽  
Pcr Amplification ◽  
Pial Surface ◽  
Migration Routes ◽  
Tangential Migration ◽  
Radial Cell ◽  
Migrating Cells

We previously reported that retrovirally marked clones in the mature chick diencephalon were widely dispersed in the mediolateral, dorsoventral and rostrocaudal planes. The current study was undertaken to define the migration routes that led to the dispersion. Embryos were infected between stages 10 and 14 with a retroviral stock encoding alkaline phosphatase and a library of molecular tags. Embryos were harvested 2.5-5.5 days later and the brains were fixed and serially sectioned. Sibling relationships were determined following PCR amplification and sequencing of the molecular tag. On embryonic day 4, all clones were organized in radial columns spanning the neuroepithelium, which was composed primarily of a ventricular zone at this age. No tangential migration was seen in the ventricular zone. On embryonic day 5, most clones remained radial with many cells located in the ventricular zone; however, a few clones had cells migrating perpendicular to the radial column, in either a rostrocaudal or dorsoventral direction. The tangential migration began just beyond the basal limit of the ventricular zone. On embryonic days 6 and 7, many clones had cells migrating perpendicular to the radial column, which spanned from the ventricular to the pial surface. The migrating cells appeared to be aligned along axes that were perpendicular to the radial column. Using a combination of DiI tracing, immunohistochemistry and electron microscopy, we have determined that axonal tracts are present and are aligned with the migrating cells, suggesting that they support the non-radial cell migration. These data indicate that migration along pathways independent of radial glia occur outside of the ventricular zone in more than 50% of the clones in the chick diencephalon.

scholarly journals Involvement of Netrins and Their Receptors in Neuronal Migration in the Cerebral Cortex

2021 ◽  
Vol 8 ◽  
Author(s):  
Satoru Yamagishi ◽  
Yuki Bando ◽  
Kohji Sato
Keyword(s):  
Neuronal Migration ◽  
Cortical Neurons ◽  
Intracellular Signaling ◽  
Ventricular Zone ◽  
Genetic Disorders ◽  
Cortical Plate ◽  
Ganglionic Eminence ◽  
Deleted In Colorectal Cancer ◽  
Guidance Molecules ◽  
Extracellular Molecules

In mammals, excitatory cortical neurons develop from the proliferative epithelium and progenitor cells in the ventricular zone and subventricular zone, and migrate radially to the cortical plate, whereas inhibitory GABAergic interneurons are born in the ganglionic eminence and migrate tangentially. The migration of newly born cortical neurons is tightly regulated by both extracellular and intracellular signaling to ensure proper positioning and projections. Non-cell-autonomous extracellular molecules, such as growth factors, axon guidance molecules, extracellular matrix, and other ligands, play a role in cortical migration, either by acting as attractants or repellents. In this article, we review the guidance molecules that act as cell–cell recognition molecules for the regulation of neuronal migration, with a focus on netrin family proteins, their receptors, and related molecules, including neogenin, repulsive guidance molecules (RGMs), Down syndrome cell adhesion molecule (DSCAM), fibronectin leucine-rich repeat transmembrane proteins (FLRTs), and draxin. Netrin proteins induce attractive and repulsive signals depending on their receptors. For example, binding of netrin-1 to deleted in colorectal cancer (DCC), possibly together with Unc5, repels migrating GABAergic neurons from the ventricular zone of the ganglionic eminence, whereas binding to α3β1 integrin promotes cortical interneuron migration. Human genetic disorders associated with these and related guidance molecules, such as congenital mirror movements, schizophrenia, and bipolar disorder, are also discussed.

scholarly journals The dynamic interplay between ATP/ADP levels and autophagy sustain neuronal migration in vivo

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Cedric Bressan ◽  
Alessandra Pecora ◽  
Dave Gagnon ◽  
Marina Snapyan ◽  
Simon Labrecque ◽  
...  
Keyword(s):  
Cell Migration ◽  
Stationary Phase ◽  
Neuronal Migration ◽  
Stationary Phases ◽  
Focal Adhesions ◽  
Time Lapse ◽  
Time Lapse Imaging ◽  
Migratory Stream ◽  
Migrating Cells

Cell migration is a dynamic process that entails extensive protein synthesis and recycling, structural remodeling, and considerable bioenergetic demand. Autophagy is one of the pathways that maintain cellular homeostasis. Time-lapse imaging of autophagosomes and ATP/ADP levels in migrating cells in the rostral migratory stream of mouse revealed that decreases in ATP levels force cells into the stationary phase and induce autophagy. Pharmacological or genetic impairments of autophagy in neuroblasts using either bafilomycin, inducible conditional mice, or CRISPR/Cas9 gene editing decreased cell migration due to the longer duration of the stationary phase. Autophagy is modulated in response to migration-promoting and inhibiting molecular cues and is required for the recycling of focal adhesions. Our results show that autophagy and energy consumption act in concert in migrating cells to dynamically regulate the pace and periodicity of the migratory and stationary phases to sustain neuronal migration.

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 Quantitative In vivo MRI Assessment of Structural Asymmetries and Sexual Dimorphism of Transient Fetal Compartments in the Human Brain

2019 ◽  
Vol 30 (3) ◽  
pp. 1752-1767 ◽  
Author(s):  
Lana Vasung ◽  
Caitlin K Rollins ◽  
Hyuk Jin Yun ◽  
Clemente Velasco-Annis ◽  
Jennings Zhang ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Brain Development ◽  
Orbitofrontal Cortex ◽  
Inferior Frontal Gyrus ◽  
Cortical Plate ◽  
Growth Trajectories ◽  
Human Cerebral Cortex ◽  
Adolescents And Adults ◽  
Cortical Regions

Abstract Structural asymmetries and sexual dimorphism of the human cerebral cortex have been identified in newborns, infants, children, adolescents, and adults. Some of these findings were linked with cognitive and neuropsychiatric disorders, which have roots in altered prenatal brain development. However, little is known about structural asymmetries or sexual dimorphism of transient fetal compartments that arise in utero. Thus, we aimed to identify structural asymmetries and sexual dimorphism in the volume of transient fetal compartments (cortical plate [CP] and subplate [SP]) across 22 regions. For this purpose, we used in vivo structural T2-weighted MRIs of 42 healthy fetuses (16.43–36.86 gestational weeks old, 15 females). We found significant leftward asymmetry in the volume of the CP and SP in the inferior frontal gyrus. The orbitofrontal cortex showed significant rightward asymmetry in the volume of CP merged with SP. Males had significantly larger volumes in regions belonging to limbic, occipital, and frontal lobes, which were driven by a significantly larger SP. Lastly, we did not observe sexual dimorphism in the growth trajectories of the CP or SP. In conclusion, these results support the hypothesis that structural asymmetries and sexual dimorphism in relative volumes of cortical regions are present during prenatal brain development.

scholarly journals In utero fate mapping reveals distinct migratory pathways and fates of neurons born in the mammalian basal forebrain

Development ◽  
2001 ◽  
Vol 128 (19) ◽  
pp. 3759-3771 ◽  
Author(s):  
Hynek Wichterle ◽  
Daniel H. Turnbull ◽  
Susana Nery ◽  
Gord Fishell ◽  
Arturo Alvarez-Buylla
Keyword(s):  
Basal Forebrain ◽  
Radial Glia ◽  
In Utero ◽  
Cortical Plate ◽  
Medium Spiny Neurons ◽  
Granule Neurons ◽  
Tangential Migration ◽  
Spiny Neurons ◽  
Developing Neocortex

Recent studies suggest that neurons born in the developing basal forebrain migrate long distances perpendicularly to radial glia and that many of these cells reach the developing neocortex. This form of tangential migration, however, has not been demonstrated in vivo, and the sites of origin, pathways of migration and final destinations of these neurons in the postnatal brain are not fully understood. Using ultrasound-guided transplantation in utero, we have mapped the migratory pathways and fates of cells born in the lateral and medial ganglionic eminences (LGE and MGE) in 13.5-day-old mouse embryos. We demonstrate that LGE and MGE cells migrate along different routes to populate distinct regions in the developing brain. We show that LGE cells migrate ventrally and anteriorly, and give rise to the projecting medium spiny neurons in the striatum, nucleus accumbens and olfactory tubercle, and to granule and periglomerular cells in the olfactory bulb. By contrast, we show that the MGE is a major source of neurons migrating dorsally and invading the developing neocortex. MGE cells migrate into the neocortex via the neocortical subventricular zone and differentiate into the transient subpial granule neurons in the marginal zone and into a stable population of GABA-, parvalbumin- or somatostatin-expressing interneurons throughout the cortical plate.

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